title: Proteolytic processing of Atg32 by the mitochondrial i-AAA protease Yme1 regulates mitophagy.
abstract: Mitophagy, the autophagic removal of mitochondria, occurs through a highly selective mechanism. In the yeast Saccharomyces cerevisiae, the mitochondrial outer membrane protein Atg32 confers selectivity for mitochondria sequestration as a cargo by the autophagic machinery through its interaction with Atg11, a scaffold protein for selective types of autophagy. The activity of mitophagy in vivo must be tightly regulated considering that mitochondria are essential organelles that produce most of the cellular energy, but also generate reactive oxygen species that can be harmful to cell physiology. We found that Atg32 was proteolytically processed at its C terminus upon mitophagy induction. Adding an epitope tag to the C terminus of Atg32 interfered with its processing and caused a mitophagy defect, suggesting the processing is required for efficient mitophagy. Furthermore, we determined that the mitochondrial i-AAA protease Yme1 mediated Atg32 processing and was required for mitophagy. Finally, we found that the interaction between Atg32 and Atg11 was significantly weakened in yme1∆ cells. We propose that the processing of Atg32 by Yme1 acts as an important regulatory mechanism of cellular mitophagy activity.
authors.affiliation: Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology; University of Michigan; Ann Arbor, MI USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Meiyan
authors.initials: M
authors.lastname: Jin
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D049069:ATP-Dependent Proteases / Q000378:metabolism*; D000071183:Autophagy-Related Proteins; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy; D008970:Molecular Weight; D011485:Protein Binding; D059748:Proteolysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C502923:Atg11 protein, S cerevisiae; C543183:Atg32 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D049069:ATP-Dependent Proteases; C082702:YME1 protein, S cerevisiae
keywords: mitochondrial protease; mitophagy; starvation; vacuole; yeast
references.citation: Mol Biol Cell. 2008 Dec;19(12):5387-97
references.pmid: 18843051
references.citation: J Cell Biol. 2010 Nov 29;191(5):933-42
references.pmid: 21115803
references.citation: EMBO J. 1989 Aug;8(8):2241-50
references.pmid: 2676517
references.citation: Autophagy. 2009 Nov;5(8):1201-2
references.pmid: 19736522
references.citation: Annu Rev Genet. 2005;39:359-407
references.pmid: 16285865
references.citation: Annu Rev Genet. 1995;29:151-78
references.pmid: 8825472
references.citation: Autophagy. 2011 Mar;7(3):297-300
references.pmid: 21252623
references.citation: Biochem Biophys Res Commun. 1995 May 5;210(1):126-32
references.pmid: 7741731
references.citation: J Cell Biol. 2008 Dec 1;183(5):795-803
references.pmid: 19029340
references.citation: J Biol Chem. 1999 Feb 19;274(8):4924-33
references.pmid: 9988735
references.citation: PLoS Biol. 2010 Jan 26;8(1):e1000298
references.pmid: 20126261
references.citation: J Biol Chem. 2012 Mar 23;287(13):10631-10638
references.pmid: 22308029
references.citation: J Biol Chem. 2012 Jan 27;287(5):3265-72
references.pmid: 22157017
references.citation: Crit Rev Biochem Mol Biol. 2007 May-Jun;42(3):221-42
references.pmid: 17562452
references.citation: EMBO J. 2008 Jan 23;27(2):306-14
references.pmid: 18216873
references.citation: Methods. 2001 Jul;24(3):218-29
references.pmid: 11403571
references.citation: FEBS Lett. 2010 Apr 2;584(7):1359-66
references.pmid: 20146925
references.citation: Mol Biol Cell. 1996 Feb;7(2):307-17
references.pmid: 8688560
references.citation: J Biophys Biochem Cytol. 1957 May 25;3(3):349-62
references.pmid: 13438920
references.citation: J Biol Chem. 2008 Nov 21;283(47):32386-93
references.pmid: 18818209
references.citation: Mol Cell. 2010 Nov 12;40(3):465-80
references.pmid: 21070972
references.citation: Cell. 2010 Jun 25;141(7):1117-34
references.pmid: 20602996
references.citation: Mol Cell Biol. 1993 Sep;13(9):5418-26
references.pmid: 8355690
references.citation: Mol Cell Biol. 2007 Apr;27(7):2476-85
references.pmid: 17261594
references.citation: Cell Death Differ. 2013 Jan;20(1):31-42
references.pmid: 22743996
references.citation: Nature. 1999 Mar 25;398(6725):348-51
references.pmid: 10192337
references.citation: Cell Death Differ. 2005 Nov;12 Suppl 2:1542-52
references.pmid: 16247502
references.citation: Science. 2011 Nov 25;334(6059):1144-7
references.pmid: 22033522
references.citation: Autophagy. 2012 Nov;8(11):1701-5
references.pmid: 22874568
references.citation: J Cell Sci. 1998 Aug;111 ( Pt 16):2455-64
references.pmid: 9683639
references.citation: Methods Enzymol. 2008;451:33-42
references.pmid: 19185711
references.citation: Mol Biol Cell. 2005 Apr;16(4):1593-605
references.pmid: 15659643
references.citation: Mol Biol Cell. 2011 Sep;22(17):3206-17
references.pmid: 21757540
references.citation: Mol Biol Cell. 2008 May;19(5):1962-75
references.pmid: 18287533
references.citation: Biochim Biophys Acta. 2012 Jan;1823(1):49-55
references.pmid: 22001671
references.citation: Methods Mol Biol. 2007;390:363-71
references.pmid: 17951700
references.citation: Dev Cell. 2009 Jul;17(1):98-109
references.pmid: 19619495
references.citation: Nature. 2008 Jul 10;454(7201):232-5
references.pmid: 18454133
references.citation: J Cell Biol. 1992 Oct;119(2):287-99
references.pmid: 1400574
references.citation: Dev Cell. 2009 Jul;17(1):87-97
references.pmid: 19619494
references.citation: Physiology (Bethesda). 2008 Oct;23:248-62
references.pmid: 18927201