m‐AAA protease‐driven membrane dislocation allows intramembrane cleavage by rhomboid in mitochondria
TLDR
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
Citations
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Journal ArticleDOI
Mode of membrane insertion of individual transmembrane segments in Mdl1 and Mdl2, multi-spanning mitochondrial ABC transporters.
TL;DR: The results show that their membrane sorting patterns differ and that specific residues in TM domains strongly influence membrane insertion or translocation, which imply that TIM23‐mediated membrane insertion highly depends on the TM domain sequence context.
Journal ArticleDOI
The Tightly Regulated and Compartmentalised Import, Sorting and Folding of Mitochondrial Proteins
Laura Cassina,Giorgio Casari +1 more
TL;DR: A survey of the function and topology of the multiple systems that operate the concerted action of protein sorting and folding in the four mitochondrial compartments.
Journal ArticleDOI
The Tightly Regulated and Compartmentalised Import, Sorting and Folding of Mitochondrial Proteins~!2009-05-06~!2009-08-12~!2010-01-02~!
Laura Cassina,Giorgio Casari +1 more
TL;DR: A survey of the function and topology of the multiple systems that operate the concerted action of protein sorting and folding in the four mitochondrial compartments.
Dissertation
Mammalian m-AAA Proteases as Key Regulators of Mitochondrial Function - Analysis of Dominant Negative Mutant Variants
TL;DR: Linking m AAA protease functions to mitochondrial fusion, cristae organization and apoptosis may help to unravel the molecular mechanisms underlying neurodegeneration associated with mutations in human m-AAA proteases.
Dissertation
Functional analysis of mammalian m-AAA proteases
TL;DR: The findings of this study indicate that the m- AAA protease has crucial functions in the regulation of mitochondrial morphology by controlling the biogenesis of OPA1 isoforms which may provide new insights into the molecular mechanisms of axonopathies caused by the loss of m-AAA protease subunits in mammals.
References
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