title: Protein quality control at the mitochondrion.
abstract: Mitochondria are essential constituents of a eukaryotic cell by supplying ATP and contributing to many mayor metabolic processes. As endosymbiotic organelles, they represent a cellular subcompartment exhibiting many autonomous functions, most importantly containing a complete endogenous machinery responsible for protein expression, folding and degradation. This article summarizes the biochemical processes and the enzymatic components that are responsible for maintaining mitochondrial protein homoeostasis. As mitochondria lack a large part of the required genetic information, most proteins are synthesized in the cytosol and imported into the organelle. After reaching their destination, polypeptides must fold and assemble into active proteins. Under pathological conditions, mitochondrial proteins become misfolded or damaged and need to be repaired with the help of molecular chaperones or eventually removed by specific proteases. Failure of these protein quality control mechanisms results in loss of mitochondrial function and structural integrity. Recently, novel mechanisms have been identified that support mitochondrial quality on the organellar level. A mitochondrial unfolded protein response allows the adaptation of chaperone and protease activities. Terminally damaged mitochondria may be removed by a variation of autophagy, termed mitophagy. An understanding of the role of protein quality control in mitochondria is highly relevant for many human pathologies, in particular neurodegenerative diseases.
authors.affiliation: Institut für Biochemie und Molekularbiologie (IBMB), Universität Bonn, Nussallee 11, D-53115 Bonn, Germany wolfgang.voos@uni-bonn.de).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
authors.affiliation: Institut für Biochemie und Molekularbiologie (IBMB), Universität Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Witold
authors.initials: W
authors.lastname: Jaworek
authors.affiliation: Institut für Biochemie und Molekularbiologie (IBMB), Universität Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Wilkening
authors.affiliation: Institut für Biochemie und Molekularbiologie (IBMB), Universität Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bruderek
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D066329:Protein Aggregates; D014176:Protein Biosynthesis; D017510:Protein Folding; D059748:Proteolysis
chemical_list: D024101:Mitochondrial Proteins; D066329:Protein Aggregates
keywords: AAA; ATP-dependent protease; ClpP; Hsp60; Hsp70; LON; mitochondria; mitochondrial unfolded protein response; mitophagy; molecular chaperones; organellar quality control; protein degradation; protein folding; protein quality control