AAA Proteases: Guardians of Mitochondrial Function and Homeostasis

Opalińska, Magdalena; Jańska, Hanna

doi:10.3390/cells7100163

Cited by 38 publications

(19 citation statements)

References 127 publications

(236 reference statements)

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“…Mitochondrial AAA proteases couple energy derived from ATP hydrolysis to versatile functions. The article by Opalinska and Janska [8] reviews the literature of AAA proteases in yeast, plants and animals and highlights the numerous roles these proteases play.…”

Section: Mitochondrial Biologymentioning

confidence: 99%

Mitochondria in Health and Disease

Annesley

Fisher

2019

Cells

318

178

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Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. They have their own genome but the great majority of the mitochondrial proteins are encoded by the nuclear genome and are imported into the mitochondria. The mitochondria participate in critical central metabolic pathways and they are fully integrated into the intracellular signalling networks that regulate diverse cellular functions. It is not surprising then that mitochondrial defects or dysregulation have emerged as having key roles in ageing and in the cytopathological mechanisms underlying cancer, neurodegenerative and other diseases. This special issue contains 12 publications—nine review articles and three original research articles. They cover diverse areas of mitochondrial biology and function and how defects in these areas can lead to disease. In addition, the articles in this issue highlight how model organisms have contributed to our understanding of these processes.

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Section: Mitochondrial Biologymentioning

confidence: 99%

Mitochondria in Health and Disease

Annesley

Fisher

2019

Cells

318

178

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“…PHBs interact with OPA1 and m -AAA proteases in order to maintain an exact cristae morphology and regulate the mitochondrial protein expression levels. Mutations in the OPA1 gene cause neurodegeneration in autosomal dominant optic atrophy [97], while mutations in m -AAA protease subunits cause spinocerebellar ataxia, hereditary spastic paraplegia, and a spastic-ataxia neuropathy syndrome [98]. It goes without saying that PHB loss can be deleterious for neuron cells.…”

Section: Pathological Role Of Prohibitinsmentioning

confidence: 99%

Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases

Signorile

Sgaramella

Bellomo

et al. 2019

Cells

142

149

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Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are proteins that are ubiquitously expressed, and are present in the nucleus, cytosol, and mitochondria. Depending on the cellular localization, PHB1 and PHB2 have distinctive functions, but more evidence suggests a critical role within mitochondria. In fact, PHB proteins are highly expressed in cells that heavily depend on mitochondrial function. In mitochondria, these two proteins assemble at the inner membrane to form a supra-macromolecular structure, which works as a scaffold for proteins and lipids regulating mitochondrial metabolism, including bioenergetics, biogenesis, and dynamics in order to determine the cell fate, death, or life. PHB alterations have been found in aging and cancer, as well as neurodegenerative, cardiac, and kidney diseases, in which significant mitochondrial impairments have been observed. The molecular mechanisms by which prohibitins regulate mitochondrial function and their role in pathology are reviewed and discussed herein.

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“…Mitochondrial ATPases associated with diverse cellular activities (AAA) proteases located in the IM are crucial for mitochondrial homeostasis and are subdivided into intermembrane space AAA (i‐AAA) proteases and matrix AAA (m‐AAA) proteases depending on the location of their active sites. In humans, m‐AAA proteases are homo‐ or hetero‐oligomeric proteins composed of ATPase family gene 3‐like protein 2 (AFG3L2) and paraplegin (Spg7), whereas i‐AAA proteases consist of homo‐oligomeric Yme1L proteins . Together with AAAs, the ATP‐independent peptidase Oma1, also located in the IM, participates in mitochondrial dynamics through the processing of Opa1 …”

Section: Introductionmentioning

confidence: 99%

“…In humans, m-AAA proteases are homo-or hetero-oligomeric proteins composed of ATPase family gene 3-like protein 2 (AFG3L2) and paraplegin (Spg7), whereas i-AAA proteases consist of homo-oligomeric Yme1L proteins. 11 Together with AAAs, the ATP-independent peptidase Oma1, also located in the IM, participates in mitochondrial dynamics through the processing of Opa1. 12 In this study, we demonstrated that muscle atrophy was closely related to an imbalance in the mitochondrial quality control system.…”

mentioning

confidence: 99%

Down‐regulation of the mitochondrial i‐AAA protease Yme1L induces muscle atrophy via FoxO3a and myostatin activation

Lee

Kim

Park

et al. 2019

J Cellular Molecular Medi

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Muscle atrophy is closely associated with many diseases, including diabetes and cardiac failure. Growing evidence has shown that mitochondrial dysfunction is related to muscle atrophy; however, the underlying mechanisms are still unclear. To elucidate how mitochondrial dysfunction causes muscle atrophy, we used hindlimb‐immobilized mice. Mitochondrial function is optimized by balancing mitochondrial dynamics, and we observed that this balance shifted towards mitochondrial fission and that MuRF1 and atrogin‐1 expression levels were elevated in these mice. We also found that the expression of yeast mitochondrial escape 1‐like ATPase (Yme1L), a mitochondrial AAA protease was significantly reduced both in hindlimb‐immobilized mice and carbonyl cyanide m‐chlorophenylhydrazone (CCCP)‐treated C2C12 myotubes. When Yme1L was depleted in myotubes, the short form of optic atrophy 1 (Opa1) accumulated, leading to mitochondrial fragmentation. Moreover, a loss of Yme1L, but not of LonP1, activated AMPK and FoxO3a and concomitantly increased MuRF1 in C2C12 myotubes. Intriguingly, the expression of myostatin, a myokine responsible for muscle protein degradation, was significantly increased by the transient knock‐down of Yme1L. Taken together, our results suggest that a deficiency in Yme1L and the consequential imbalance in mitochondrial dynamics result in the activation of FoxO3a and myostatin, which contribute to the pathological state of muscle atrophy.

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AAA Proteases: Guardians of Mitochondrial Function and Homeostasis

Cited by 38 publications

References 127 publications

Mitochondria in Health and Disease

Mitochondria in Health and Disease

Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases

Down‐regulation of the mitochondrial i‐AAA protease Yme1L induces muscle atrophy via FoxO3a and myostatin activation

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