- Staffordshire University, Biological Sciences, Faculty Memberadd
- Mitochondria, Apoptosis, Cytochrome c oxidase, Mitochondrial DNA, Mitochondrial Medicine, Mitochondrial Evolution, and 38 moreMitochondrial Diseases, Mitochondrial dysfunction, Mitochondria biogenesis, Mitochondrial Ribosomes, Mitochondria, Energy metabolism, Metabolic disease, Mitochondria-Nucleus Crosstalk, Mitochondria, Calcium Signaling, Mitochondrial Dynamics, Oxidative stress and mitochondria, Mitochondrial disease, Mitochondria, cancer & cell signalling, Mitochondrial, Biological Sciences, Oxidative Stress, Cell death mechanisms, Caspases, Cyclosporine, Sanglifherin A, Bimolecular Fluorescence Complementation, Heat Shock, Adenine Nucleotide Translocase, Mitochondrial Permeability Transition Pore, Biochemistry, Pharmacology, Antioxidants, Biology, Genomics, Cancer Biology, Transcription Factors, Breast Cancer, Gene expression, Parkinson's Disease, Gene Therapy, Neurodegenerative Diseases, Neurodegeneration, Cell Biology, Molecular Biology, and Medicineedit
- Studies mitochondrial physiology and cell death.edit
Research Interests:
Maintaining mitochondrial homeostasis and energy metabolism is essential for normal cardiac function. Adenosine-monophosphate activated protein kinase (AMPK) is an energy sensor in the cell that detects and reacts to fluctuations in... more
Maintaining mitochondrial homeostasis and energy metabolism is essential for normal cardiac function. Adenosine-monophosphate activated protein kinase (AMPK) is an energy sensor in the cell that detects and reacts to fluctuations in intracellular AMP: ATP ratio and it is activated by increased AMP levels. Activated AMPK promotes ATP production by inhibiting anabolic consuming pathways and enhancing catabolic pathways. AMPK has been shown to protect the heart under several cardiac conditions including ischemia and starvation. The cardioprotective effects have been attributed partially to its ability to induce autophagy, a cellular degradation pathway that eliminates protein aggregates and damaged organelles through the lysosome. When mitochondria are targeted for degradation through autophagy, it is termed mitophagy. Both autophagy and mitophagy may occur under the same conditions but they do not always go in the same direction, suggesting that they may be regulated by distinct pathways. Despite its ability to positively regulate autophagy, AMPK has not been shown to directly regulate mitophagy. In the present study, we investigated if AMPK is required for mitophagy in the heart using mice that lack AMPK alpha 2 gene (knockout, KO) and express a novel mitophagy reporter known as mito-Rosella, a dual-emission biosensor composed of a mitochondrial targeting sequence and a RFP-GFP fusion protein. Mitophagy events were seen as red puncta on merged confocal microscopic images. These red puncta represent mitochondrial fragments that are being degraded in lysosomes where the pH sensitive GFP is quenched. To assess mitophagy flux, these mice were also treated with lysosomal protease inhibitors pepstatin A and E64-d, which lead to an accumulation of red puncta in mitolysosomes. To our surprise, AMPK alpha 2 KO mouse hearts had markedly increased amount of red puncta than wild type hearts, the number of which was further increased by the lysosomal protease inhibitors, suggesting an enhanced mitophagy flux in the absence of AMPK alpha 2 gene. Consistently, western blot analysis showed significantly increased autophagy marker protein LC3-II in AMPK alpha 2 KO mouse hearts. These findings were confirmed in H9c2 cardiac myoblast cells treated with siRNAs targeting both AMPK alpha 1 and alpha 2 genes. In addition, the protein expression levels of FUN14 domain containing 1 (FUNDC1), a positive regulator of mitophagy, were up-regulated in the AMPK alpha 2 KO hearts, which may contribute to the enhanced mitophagy. Collectively, these results suggest that AMPK is a negative regulator of mitophagy, contrary to the widely held hypothesis that AMPK signalling is necessary for mitophagy. Future studies are warranted to investigate if AMPK over expression can inhibit mitophagy either at basal level or in response to various cardiac stresses.
Research Interests:
Small molecules are optimally lipophilic in nature, which allows for transit through the circulation by binding to plasma proteins and passage through cellular membranes to gain access to intracellular targets. The molecular composition... more
Small molecules are optimally lipophilic in nature, which allows for transit through the circulation by binding to plasma proteins and passage through cellular membranes to gain access to intracellular targets. The molecular composition and architecture of mitochondria is also responsible for attracting certain small molecules that results in accumulation and impact on mitochondrial function. Binding to plasma protein provides a reservoir of the drug capable of providing a longer‐lasting reservoir of the drug compared with those more freely soluble in the bloodstream and may eventually accumulate in target tissues to a greater extent than the latter more hydrophilic drugs. Molecules transported by albumin are released in regions of low drug concentration. This mechanism enables drugs to be delivered to target tissues and enter into cells either by transport through specific plasma membrane transporters or via diffusion through the plasma membrane.
Research Interests: Chemistry, Drug, Albumin, Membrane, Transporter, and 3 moreProtein Transport, Intracellular, and Mitochondrion
Research Interests:
Research Interests: Biochemistry, Chemistry, Biology, Membrane Proteins, Mitochondria, and 14 moreTranscription Factors, Medicine, Western blotting, Saccharomyces cerevisiae, Mutation, Cytochrome C, Cytochrome c oxidase, Ribosomal proteins, Two-Dimensional Gel Electrophoresis, Protein Binding, Protein Biosynthesis, Biochemistry and cell biology, Mitochondrion, and Mitochondrial Proteins
Research Interests: Biochemistry, Chemistry, Biology, Mitochondria, Biological Chemistry, and 15 moreMedicine, Biological Sciences, Mitochondria biogenesis, Saccharomyces cerevisiae, Mitochondrial DNA, Mutation, Cytochrome c oxidase, Yeast, Biogenesis, MITOCHONDRIAL BIOGENESIS, CHEMICAL SCIENCES, Cell nucleus, Mitochondrion, alleles, and Medical and Health Sciences
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Small-molecule inhibitors of caspases can be modified with moieties such as biotin or fluorescent molecules. After the inhibitor molecule has bound to an active caspase, the caspase itself becomes labeled and can be isolated using... more
Small-molecule inhibitors of caspases can be modified with moieties such as biotin or fluorescent molecules. After the inhibitor molecule has bound to an active caspase, the caspase itself becomes labeled and can be isolated using affinity purification. This protocol describes the use of the biotinylated pan-caspase inhibitor VAD-FMK and streptavidin beads to isolate active caspases. These caspases are then separated by gel electrophoresis and identified with caspase-specific antibodies using western blotting techniques. Other caspase inhibitors bound with biotin or other labels can be substituted in this assay; labeled inhibitors are available commercially as either pan-caspase or caspase-specific probes.
Research Interests:
Research Interests:
Research Interests: Biochemistry, Biology, Mitochondria, Biological Chemistry, Medicine, and 15 moreBiological Sciences, Saccharomyces cerevisiae, Mitochondrial DNA, Glucose, Mutation, ATP synthase, Phosphorylation, CHEMICAL SCIENCES, Genotype, Oxygen, Oxidative phosphorylation, Adenosine Triphosphate, Mitochondrion, ATP hydrolysis, and Medical and Health Sciences
Research Interests:
Monitoring the activity of a caspase, either as an isolated protein or in a complex mixture (e.g., a cytosolic extract), can be achieved by measuring substrate cleavage. Chromogenic or fluorogenic substrates are available for many... more
Monitoring the activity of a caspase, either as an isolated protein or in a complex mixture (e.g., a cytosolic extract), can be achieved by measuring substrate cleavage. Chromogenic or fluorogenic substrates are available for many caspases. These substrates usually consist of the four-amino-acid motif that is optimal for each caspase and a moiety that, when cleaved, generates either a chromophore or a fluorophore that can be detected using spectrophotometric or fluorimetric means. In this protocol, we describe how to use these substrates to monitor caspase activity in samples containing active caspases (e.g., apoptotic cells). Caspase inhibitors, which contain a moiety that covalently attaches to the active site of the caspase, can be used in these assays. These assays will ascertain whether caspases are involved in a specific process (e.g., whether caspases are activated after an apoptotic stimulus) and are particularly informative if a purified caspase is used. However, the substrates and inhibitors are not specific for a particular caspase in an environment containing multiple caspases. So, if cytosolic or apoptotic cell extracts are used in these assays, additional experiments must be performed to identify exactly which caspases are involved.
Research Interests:
Proteomic approaches have been adopted to survey the degradome of caspases during apoptosis. These approaches provide a comprehensive list of substrates and give clues to which pathways are altered during apoptosis by activated caspases.... more
Proteomic approaches have been adopted to survey the degradome of caspases during apoptosis. These approaches provide a comprehensive list of substrates and give clues to which pathways are altered during apoptosis by activated caspases. However, substrates identified by large-scale proteomic screening need to be validated as bona fide caspase targets. This ensures that conclusions derived from the screen are based on real substrates and not on artifacts of the proteomic screen. The validation method described in this protocol uses radiolabeled versions of the putative substrates synthesized using in vitro transcription/translation methods. These are incubated with purified caspases to determine whether they are genuine caspase substrates.
Research Interests:
Research Interests:
Caspases are proteases that are essential components of apoptotic cell death pathways. There are approximately one dozen apoptotic caspases found in organisms where cells die via apoptosis. These caspases are responsible for initiation or... more
Caspases are proteases that are essential components of apoptotic cell death pathways. There are approximately one dozen apoptotic caspases found in organisms where cells die via apoptosis. These caspases are responsible for initiation or execution of apoptosis through the proteolytic cleavage of specific substrates. These substrates contain specific motifs that are recognized and cleaved by caspases that result in alterations of substrate function that promotes the apoptotic phenotype. Analysis of caspase involvement, much like any other protease, can be followed using peptides corresponding to cleavage motifs of these substrates, which can be used as substrates, inhibitors, or affinity-based probes.Different caspases have different substrates and therefore different motifs are recognized by each different caspase. However, these different caspases have a common amino acid recognition pattern containing an aspartic acid residue at the amino-side of the cleavage site. Therefore, caspase substrates have a certain overlap in the cleavage motif as this aspartic acid is found in almost every one. This means that certain peptide motifs are not exclusively cleaved by one single caspase. This lack of exclusive cleavage has brought the use of these motif-based probes into question and spurred the development of truly caspase-specific motifs. This chapter describes the use of peptide-based probes to measure caspase activity while highlighting the limitations of these reagents.
Research Interests:
It can be useful to explore the caspase activation process in an in vitro setting. In this protocol, cytosolic extracts prepared from cell culture are incubated with cytochrome c and adenosine triphosphate (dATP), leading to the... more
It can be useful to explore the caspase activation process in an in vitro setting. In this protocol, cytosolic extracts prepared from cell culture are incubated with cytochrome c and adenosine triphosphate (dATP), leading to the oligomerization of apoptotic protease activating factor-1 (APAF-1) and the formation of the apoptosome. The apoptosome serves as an activation platform for caspase-9, which binds to the apoptosome through heterodimeric caspase recruitment domain (CARD) interactions and then dimerizes. This leads to cleavage of the executioner, caspase-3. These extracts contain highly active caspases that can be analyzed using a variety of biochemical assays.
Research Interests:
A number of antibodies have been generated that recognize caspases from mammalian model organisms. These include antibodies that recognize specific caspase pro-forms and others that bind caspase cleavage fragments. These antibodies are... more
A number of antibodies have been generated that recognize caspases from mammalian model organisms. These include antibodies that recognize specific caspase pro-forms and others that bind caspase cleavage fragments. These antibodies are excellent reagents for identifying which executioner caspases have been activated following application or induction of a specific apoptotic stimulus. This approach is more difficult to use with initiator caspases, however, because cleavage does not necessarily correlate with caspase activation. In this protocol, cultured cells are treated with a proapoptotic stimulus, and then protein lysates are prepared from the treated cells. The proteins are then separated by gel electrophoresis and transferred to a suitable membrane. The fragment-specific antibodies that recognize executioner caspases are used in a western analysis to determine the extent of activation and to aid in identifying which caspases have been activated.
Research Interests:
Caspases are proteases that are responsible for the initiation and execution of cell death pathways in developmental, inflammatory and pharmacological paradigms. Caspase activity is required for the execution of apoptotic cell death... more
Caspases are proteases that are responsible for the initiation and execution of cell death pathways in developmental, inflammatory and pharmacological paradigms. Caspase activity is required for the execution of apoptotic cell death through the proteolytic cleavage of approximately one thousand substrates that result in the apoptotic phenotype. Impaired executioner caspase activity leads to delayed cell death and persistence of damaged cells that may impact overall organismal health. This is especially true in the case of cancer, impaired executioner caspase activity prevents execution of cell death and cells persist potentially leading to the formation or maintenance of tumors or lack of responsiveness to chemotherapeutic agents. Impairment of executioner activity can arise due to alterations in caspase expression, mutation in the caspase or alterations in caspase regulators. Here the human executioner caspases will be considered with specific focus on how expression and activity of caspase-3, -6, and -7 are altered in cancer.
Research Interests:
Research Interests:
Research Interests:
Cytochrome c oxidase is the terminal electron acceptor in the electron transport chain in many aerobic organisms. This multi-protein complex can be composed of a varying number of subunits depending on species. In the budding yeast,... more
Cytochrome c oxidase is the terminal electron acceptor in the electron transport chain in many aerobic organisms. This multi-protein complex can be composed of a varying number of subunits depending on species. In the budding yeast, Saccharomyces cerevisiae, cytochrome c oxidase is made up of 11 subunits, 8 are derived from the nuclear genome and 3 are derived from the mitochondrial genome. To ensure these subunits come together at the correct time and place a family of assembly factors is required. In the case of the mitochondrial DNA encoded subunit 1 there is a linear pathway of biosynthesis where these assembly factors and other structural subunits associate at specific times to regulate specific maturation events. In the absence of some assembly factors subunit 1 is subject to degradation by the protease Oma1p. In yeast, this results in a deficiency in cytochrome c oxidase activity and the inability to grow using substrates requiring intact oxidative phosphorylation. We have performed a mutagenic screen of mitochondrial DNA to identify mutations in the subunit 1 gene that can suppress the oxidative phosphorylation deficient phenotype caused by the absence of the assembly factors, COA2 and SHY1. Through analysis of the COX1 gene we will identify putative regions required for the proteolytic processing of subunit 1 by the Oma1p protease. The information gathered from this research will guide us in identifying putative regions required for cytochrome c oxidase subunit 1 degradation and also provide more information regarding the proteolytic requirements of the Oma1p protease.
Research Interests:
Research Interests:
Research Interests: Biophysics, Biology, Calcium, Cell Biology, Mitochondria, and 15 moreMedicine, Ion Channels, Humans, Animals, Cell Death, Biochimie, Mode of action, Mitochondrial Permeability Transition Pore, Adenine Nucleotide Translocase, Conformational Change, Biochemistry and cell biology, Binding affinity, Mitochondrion, Cell membrane permeability, and MPTP
Research Interests:
Research Interests: Biochemistry, Chemistry, Mitochondria, Medicine, Biological Sciences, and 15 moreAnimals, Ant, Male, Glutathione, Biochemical, Affinity chromatography, CHEMICAL SCIENCES, Cysteine, Glutathione Transferase, Mitochondrial Permeability Transition Pore, Adenine Nucleotide Translocase, Arsenicals, Dimerization, Adenosine Diphosphate, and Medical and Health Sciences
Research Interests:
Research Interests:
Small molecules are optimally lipophilic in nature, which allows for transit through the circulation by binding to plasma proteins and passage through cellular membranes to gain access to intracellular targets. The molecular composition... more
Small molecules are optimally lipophilic in nature, which allows for transit through the circulation by binding to plasma proteins and passage through cellular membranes to gain access to intracellular targets. The molecular composition and architecture of mitochondria is also responsible for attracting certain small molecules that results in accumulation and impact on mitochondrial function. Binding to plasma protein provides a reservoir of the drug capable of providing a longer‐lasting reservoir of the drug compared with those more freely soluble in the bloodstream and may eventually accumulate in target tissues to a greater extent than the latter more hydrophilic drugs. Molecules transported by albumin are released in regions of low drug concentration. This mechanism enables drugs to be delivered to target tissues and enter into cells either by transport through specific plasma membrane transporters or via diffusion through the plasma membrane.
Research Interests:
Maintaining mitochondrial homeostasis and energy metabolism is essential for normal cardiac function. Adenosine-monophosphate activated protein kinase (AMPK) is an energy sensor in the cell that detects and reacts to fluctuations in... more
Maintaining mitochondrial homeostasis and energy metabolism is essential for normal cardiac function. Adenosine-monophosphate activated protein kinase (AMPK) is an energy sensor in the cell that detects and reacts to fluctuations in intracellular AMP: ATP ratio and it is activated by increased AMP levels. Activated AMPK promotes ATP production by inhibiting anabolic consuming pathways and enhancing catabolic pathways. AMPK has been shown to protect the heart under several cardiac conditions including ischemia and starvation. The cardioprotective effects have been attributed partially to its ability to induce autophagy, a cellular degradation pathway that eliminates protein aggregates and damaged organelles through the lysosome. When mitochondria are targeted for degradation through autophagy, it is termed mitophagy. Both autophagy and mitophagy may occur under the same conditions but they do not always go in the same direction, suggesting that they may be regulated by distinct pathw...
Research Interests:
Research Interests:
Bcl-2 interacts with tBid thereby sequestering tBid in stable mitochondrial complexes and preventing its association with and subsequent activation of Bax or Bak (Wang et al., 1996; Cheng et al., 2001). Recently, it has been shown that... more
Bcl-2 interacts with tBid thereby sequestering tBid in stable mitochondrial complexes and preventing its association with and subsequent activation of Bax or Bak (Wang et al., 1996; Cheng et al., 2001). Recently, it has been shown that Bid-BH3 peptides bind moderately to Bcl-2 (Letai et al., 2002; Chen et al., 2005).
Research Interests:
Research Interests:
Journal of Molecular and Cellular Cardiology, Volume 34, Issue 6, Pages A17, June 2002, Authors:Samantha J. Clarke; Gavin P. McStay; Andrew P. Halestrap.
Research Interests:
Opening of the mitochondrial permeability transition pore (MPTP) is sensitized to [Ca2+] by oxidative stress (diamide) and phenylarsine oxide (PAO). We have proposed that both agents cross-link two thiol groups on the adenine nucleotide... more
Opening of the mitochondrial permeability transition pore (MPTP) is sensitized to [Ca2+] by oxidative stress (diamide) and phenylarsine oxide (PAO). We have proposed that both agents cross-link two thiol groups on the adenine nucleotide translocase (ANT) involved in ADP and cyclophilin-D (CyP-D) binding. Here, we demonstrate that blocking Cys160 with 80μM eosin 5-maleimide (EMA) or 500μM N-ethylmaleimide (NEM) greatly decreased ADP inhibition of the MPTP. The ability of diamide, but not PAO, to block ADP inhibition of the MPTP was antagonized by treatment of mitochondria with 50μM NEM to alkylate matrix glutathione. Binding of detergent-solubilized ANT to a PAO-affinity matrix was prevented by pre-treatment of mitochondria with diamide, EMA or PAO, but not NEM. EMA binding to the ANT in submitochondrial particles (SMPs) was prevented by pre-treatment of mitochondria with either PAO or diamide, implying that both agents modify Cys160. Diamide and PAO pre-treatments also inhibited bin...
Research Interests: Chemistry, Oxidative Stress, Mitochondria, Medicine, Biological Sciences, and 15 morePermeability, Animals, Male, Biochemical, Affinity chromatography, CHEMICAL SCIENCES, Rats, Cysteine, Glutathione Transferase, Mitochondrial Permeability Transition Pore, Adenine Nucleotide Translocase, Arsenicals, Dimerization, Adenosine Diphosphate, and Medical and Health Sciences
Research Interests:
Caspases are proteases that are responsible for the initiation and execution of cell death pathways in developmental, inflammatory and pharmacological paradigms. Caspase activity is required for the execution of apoptotic cell death... more
Caspases are proteases that are responsible for the initiation and execution of cell death pathways in developmental, inflammatory and pharmacological paradigms. Caspase activity is required for the execution of apoptotic cell death through the proteolytic cleavage of approximately one thousand substrates that result in the apoptotic phenotype. Impaired executioner caspase activity leads to delayed cell death and persistence of damaged cells that may impact overall organismal health. This is especially true in the case of cancer, impaired executioner caspase activity prevents execution of cell death and cells persist potentially leading to the formation or maintenance of tumors or lack of responsiveness to chemotherapeutic agents. Impairment of executioner activity can arise due to alterations in caspase expression, mutation in the caspase or alterations in caspase regulators. Here the human executioner caspases will be considered with specific focus on how expression and activity o...
Research Interests:
Mitochondrial function relies on the function of oxidative phosphorylation to synthesise ATP and generate an electrochemical gradient across the inner mitochondrial membrane. These coupled processes are mediated by five multi-subunit... more
Mitochondrial function relies on the function of oxidative phosphorylation to synthesise ATP and generate an electrochemical gradient across the inner mitochondrial membrane. These coupled processes are mediated by five multi-subunit complexes that reside in this inner membrane. These complexes are the product of both nuclear and mitochondrial gene products. Defects in the function or assembly of these complexes can lead to mitochondrial diseases due to deficits in energy production and mitochondrial functions. Appropriate biogenesis and function are mediated by a complex number of assembly factors that promote maturation of specific complex subunits to form the active oxidative phosphorylation complex. The understanding of the biogenesis of each complex has been informed by studies in both simple eukaryotes such as Saccharomyces cerevisiae and human patients with mitochondrial diseases. These studies reveal each complex assembles through a pathway using specific subunits and assembly factors to form kinetically distinct but related assembly modules. The current understanding of these complexes has embraced the revolutions in genomics and proteomics to further our knowledge on the impact of mitochondrial biology in genetics, medicine, and evolution.
Research Interests:
Cytochrome c oxidase is the terminal complex of eukaryotic oxidative phosphorylation in mitochondria. This process couples the reduction of electron carriers during metabolism to the reduction of molecular oxygen to water and... more
Cytochrome c oxidase is the terminal complex of eukaryotic oxidative phosphorylation in mitochondria. This process couples the reduction of electron carriers during metabolism to the reduction of molecular oxygen to water and translocation of protons from the internal mitochondrial matrix to the inter-membrane space. The electrochemical gradient formed is used to generate chemical energy in the form of adenosine triphosphate to power vital cellular processes. Cytochrome c oxidase and most oxidative phosphorylation complexes are the product of the nuclear and mitochondrial genomes. This poses a series of topological and temporal steps that must be completed to ensure efficient assembly of the functional enzyme. Many assembly factors have evolved to perform these steps for insertion of protein into the inner mitochondrial membrane, maturation of the polypeptide, incorporation of co-factors and prosthetic groups and to regulate this process. Much of the information about each of these ...
Research Interests:
Cytochrome oxidase (COX) is a hetero-oligomeric complex of the mitochondrial inner membrane that reduces molecular oxygen to water, a reaction coupled to proton transfer from the mitochondrial matrix to the intermembrane space. In the... more
Cytochrome oxidase (COX) is a hetero-oligomeric complex of the mitochondrial inner membrane that reduces molecular oxygen to water, a reaction coupled to proton transfer from the mitochondrial matrix to the intermembrane space. In the yeast Saccharomyces cerevisiae, COX is composed of 11-13 different polypeptide subunits. Here, using pulse labeling of mitochondrial gene products in isolated yeast mitochondria, combined with purification of tagged COX subunits and ancillary factors, we studied the Cox2p assembly intermediates. Analysis of radiolabeled Cox2p obtained in pull-down assays by native gel electrophoresis revealed the existence of several assembly intermediates, the largest of which having an estimated mass of 450-550 kDa. None of the other known subunits of COX were present in these Cox2p intermediates. This was also true for the several ancillary factors having still undefined functions in COX assembly. In agreement with earlier evidence, Cox18p and Cox20p, previously sho...
Research Interests:
The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as adenosine triphosphate (ATP) synthesis, central metabolism, apoptosis and inflammation.... more
The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as adenosine triphosphate (ATP) synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside in or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space. Mitochondrial fission and fusion are performed by guanosine triphosphatases (GTPases) on the outer and inner mitochondrial membranes with the assistance of other mitochondrial proteins. Due to the essential nature of mitochondrial function for cellular homeostasis, regulation of mitochondrial dynamics is under strict control. Some of the mechanisms used to regulate the function of these proteins are post-t...