title: Uth1 is a mitochondrial inner membrane protein dispensable for post-log-phase and rapamycin-induced mitophagy.
abstract: Mitochondria are turned over by an autophagic process termed mitophagy. This process is considered to remove damaged, superfluous and aged organelles. However, little is known about how defective organelles are recognized, what types of damage induce turnover, and whether an identical set of factors contributes to degradation under different conditions. Here we systematically compared the mitophagy rate and requirement for mitophagy-specific proteins during post-log-phase and rapamycin-induced mitophagy. To specifically assess mitophagy of damaged mitochondria, we analyzed cells accumulating proteins prone to degradation due to lack of the mitochondrial AAA-protease Yme1. While autophagy 32 (Atg32) was required under all tested conditions, the function of Atg33 could be partially bypassed in post-log-phase and rapamycin-induced mitophagy. Unexpectedly, we found that Uth1 was dispensable for mitophagy. A re-evaluation of its mitochondrial localization revealed that Uth1 is a protein of the inner mitochondrial membrane that is targeted by a cleavable N-terminal pre-sequence. In agreement with our functional analyses, this finding excludes a role of Uth1 as a mitochondrial surface receptor.
authors.affiliation: Department of Cellular Biochemistry, Georg-August University, Göttingen, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Welter
authors.forename: Marco
authors.initials: M
authors.lastname: Montino
authors.forename: Robert
authors.initials: R
authors.lastname: Reinhold
authors.forename: Petra
authors.initials: P
authors.lastname: Schlotterhose
authors.forename: Roswitha
authors.initials: R
authors.lastname: Krick
authors.forename: Jan
authors.initials: J
authors.lastname: Dudek
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.forename: Michael
authors.initials: M
authors.lastname: Thumm
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D063306:Mitophagy / Q000187:drug effects*; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C116477:UTH1 protein, S cerevisiae; D020123:Sirolimus
keywords: Atg32; Atg33; Saccharomyces cerevisiae; Uth1; Yme1; macroautophagy; mitophagy