Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness

Uwe Richter; Taina Lahtinen; Paula Marttinen; Fumi Suomi; Brendan J Battersby

doi:10.1083/jcb.201504062

Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness

J Cell Biol. 2015 Oct 26;211(2):373-89. doi: 10.1083/jcb.201504062.

Authors

Uwe Richter¹, Taina Lahtinen¹, Paula Marttinen¹, Fumi Suomi¹, Brendan J Battersby²

Affiliations

¹ Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
² Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland brendan.battersby@helsinki.fi.

Abstract

Mitochondrial ribosomes synthesize a subset of hydrophobic proteins required for assembly of the oxidative phosphorylation complexes. This process requires temporal and spatial coordination and regulation, so quality control of mitochondrial protein synthesis is paramount to maintain proteostasis. We show how impaired turnover of de novo mitochondrial proteins leads to aberrant protein accumulation in the mitochondrial inner membrane. This creates a stress in the inner membrane that progressively dissipates the mitochondrial membrane potential, which in turn stalls mitochondrial protein synthesis and fragments the mitochondrial network. The mitochondrial m-AAA protease subunit AFG3L2 is critical to this surveillance mechanism that we propose acts as a sensor to couple the synthesis of mitochondrial proteins with organelle fitness, thus ensuring coordinated assembly of the oxidative phosphorylation complexes from two sets of ribosomes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP-Dependent Proteases / genetics
ATP-Dependent Proteases / metabolism*
ATPases Associated with Diverse Cellular Activities
Amidohydrolases / genetics
Amidohydrolases / metabolism
Animals
Cell Line
Cell Membrane / physiology
HEK293 Cells
Humans
Hydroxamic Acids / pharmacology
Membrane Potential, Mitochondrial / physiology
Metalloproteases / genetics
Metalloproteases / metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mitochondria / metabolism*
Mitochondrial Membranes / pathology*
Mitochondrial Proteins / biosynthesis*
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Mitochondrial Proton-Translocating ATPases / genetics
Oxidative Phosphorylation
Oxidative Phosphorylation Coupling Factors / biosynthesis
Protein Biosynthesis / genetics
RNA Interference
RNA, Small Interfering

Substances

Hydroxamic Acids
Mitochondrial Proteins
Oxidative Phosphorylation Coupling Factors
RNA, Small Interfering
Metalloproteases
OMA1 protein, mouse
ATP-Dependent Proteases
Afg3l2 protein, mouse
Amidohydrolases
peptide deformylase
ATP5b protein, mouse
Mitochondrial Proton-Translocating ATPases
ATPases Associated with Diverse Cellular Activities
actinonin