m‐AAA protease‐driven membrane dislocation allows intramembrane cleavage by rhomboid in mitochondria
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Findings reveal for the first time a non‐proteolytic function of the m‐AAA protease during mitochondrial biogenesis and rationalise the requirement of a preceding step for intramembrane cleavage by rhomboid.Abstract:
Maturation of cytochrome c peroxidase (Ccp1) in mitochondria occurs by the subsequent action of two conserved proteases in the inner membrane: the m-AAA protease, an ATP-dependent protease degrading misfolded proteins and mediating protein processing, and the rhomboid protease Pcp1, an intramembrane cleaving peptidase. Neither the determinants preventing complete proteolysis of certain substrates by the m-AAA protease, nor the obligatory requirement of the m-AAA protease for rhomboid cleavage is currently understood. Here, we describe an intimate and unexpected functional interplay of both proteases. The m-AAA protease mediates the ATP-dependent membrane dislocation of Ccp1 independent of its proteolytic activity. It thereby ensures the correct positioning of Ccp1 within the membrane bilayer allowing intramembrane cleavage by rhomboid. Decreasing the hydrophobicity of the Ccp1 transmembrane segment facilitates its dislocation from the membrane and renders rhomboid cleavage m-AAA protease-independent. These findings reveal for the first time a non-proteolytic function of the m-AAA protease during mitochondrial biogenesis and rationalise the requirement of a preceding step for intramembrane cleavage by rhomboid.read more
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Dissertation
A mitochondrial profile in a mouse model of dominant optic atrophy
TL;DR: The study of mitochondrial haploinsufficiency with analysis of OXPHOS and antioxidant levels in Opa1Q285STOP mouse where a bioenergetic deficit was identified in all mitochondria tested and the status of antioxidant activity supportingBioenergetic function may be vital in maintaining stability within fusion deficient mitochondria.
Book ChapterDOI
Quality Control and Quality Assurance in the Mitochondrion
TL;DR: Future work holds the promise of delineating the roles of mitochondrial ATP dependent proteases and chaperones not only in cellular metabolism and general physiology, but also in disease states such as neurodegeneration and cancer, or aging.
Dissertation
Role of the AAA protease Yme1 in folding of proteins in the mitochondrial intermembrane space
TL;DR: Yme1 thus has a dual role as protease and as chaperone and occupies a key position in the protein quality control system of the mitochondrial intermembrane space.
References
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Journal ArticleDOI
AAA+ proteins: have engine, will work.
TL;DR: The structural organization of AAA+ proteins, the conformational changes they undergo, the range of different reactions they catalyse, and the diseases associated with their dysfunction are reviewed.
Journal ArticleDOI
Proteolysis: from the lysosome to ubiquitin and the proteasome.
TL;DR: In this paper, the ubiquitin-proteasome system resolved the enigma of how cellular proteins are degraded in the lysosome and showed that non-lysosomal pathways have an important role in intracellular proteolysis, although their identity and mechanisms of action remained obscure.
Journal ArticleDOI
Regulation of mitochondrial morphology through proteolytic cleavage of OPA1.
TL;DR: M mammalian mitochondrial function and morphology is regulated through processing of OPA1 in a ΔΨ‐dependent manner through proteolytic cleavage of Mgm1, the yeast homolog of O PA1.
Journal ArticleDOI
Solvation Energies of Amino Acid Side Chains and Backbone in a Family of Host−Guest Pentapeptides
TL;DR: The very large peptide bond ASP, -96 +/- 6 cal/mol/A2, profoundly affects the results of computational comparisons of protein stability which use ASPs derived from octanol-water partitioning data.
Journal ArticleDOI
Sculpting the Proteome with AAA+ Proteases and Disassembly Machines
Robert T. Sauer,Daniel N. Bolon,Briana M. Burton,Randall E. Burton,Julia M. Flynn,Robert A. Grant,Greg L. Hersch,Shilpa A. Joshi,Jon A. Kenniston,Igor Levchenko,Saskia B. Neher,Elizabeth S.C. Oakes,Samia M. Siddiqui,David A. Wah,Tania A. Baker +14 more
TL;DR: Exciting progress has been made in understanding how AAA(+) machines recognize specific proteins as targets and then carry out ATP-dependent dismantling of the tertiary and/or quaternary structure of these molecules during the processes of protein degradation and the disassembly of macromolecular complexes.