KEGG   PATHWAY: sce04139
Entry
sce04139                    Pathway                                
Name
Mitophagy - yeast - Saccharomyces cerevisiae (budding yeast)
Description
Mitophagy, which refers to the selective elimination of impaired or excessive mitochondria, is considered to be the main mechanism for mitochondria quality and quantity control. In yeast, oxidative stress or inhibition of TOR induces expression of Agt32, the indispensable mitochondrial outer membrane receptor. Direct phosphorylation of Atg32 by CK2 triggers mitophagy, and two mitogen-activated protein kinase (MAPK) signal transduction pathways are also important in this process. Atg11 is an adaptor protein for selective autophagy, and recruits the cargo to the phagophore assembly site (PAS), where the autophagosome is generated. Then Atg32-Atg8 interaction enhances the formation of the autophagosome surrounding the mitochondria, which finally fuses with vacuoles for degradation. Atg32-Atg11 interaction may also be regulated by Yme1-mediated processing of Atg32, as well as by mitochondrial fission machinery. Some factors have been suggested to positively or negatively regulate the mitophagy via different mechanisms, including Atg1, Atg33, Mss4, Fmc1, Mdm38, Mip1, and Ubp3-Bre5 deubiquitination complex.
Class
Cellular Processes; Transport and catabolism
Pathway map
sce04139  Mitophagy - yeast
sce04139

Other DBs
GO: 0000422
Organism
Saccharomyces cerevisiae (budding yeast) [GN:sce]
Gene
YJR066W  TOR1; phosphatidylinositol kinase-related protein kinase TOR1 [KO:K07203] [EC:2.7.11.1]
YKL203C  TOR2; phosphatidylinositol kinase-related protein kinase TOR2 [KO:K07203] [EC:2.7.11.1]
YLR147C  SMD3; mRNA splicing protein SMD3 [KO:K11088]
YOL004W  SIN3; transcriptional regulator SIN3 [KO:K11644]
YDR207C  UME6; DNA-binding transcriptional regulator UME6 [KO:K09243]
YIL146C  ATG32; mitophagy protein ATG32 [KO:K17984]
YPR024W  YME1; i-AAA protease YME1 [KO:K08955] [EC:3.4.24.-]
YNL283C  WSC2; Wsc2p [KO:K11244]
YOR008C  SLG1; Slg1p [KO:K11244]
YOL105C  WSC3; Wsc3p [KO:K11244]
YBL105C  PKC1; protein kinase C [KO:K02677] [EC:2.7.11.13]
YJL095W  BCK1; mitogen-activated protein kinase kinase kinase BCK1 [KO:K11229] [EC:2.7.11.25]
YOR231W  MKK1; mitogen-activated protein kinase kinase MKK1 [KO:K08294] [EC:2.7.12.2]
YPL140C  MKK2; putative mitogen-activated protein kinase kinase MKK2 [KO:K08294] [EC:2.7.12.2]
YHR030C  SLT2; mitogen-activated serine/threonine-protein kinase SLT2 [KO:K04464] [EC:2.7.11.24]
YIL147C  SLN1; histidine kinase [KO:K11231] [EC:2.7.13.3]
YLR006C  SSK1; mitogen-activated protein kinase kinase kinase SSK1 [KO:K11233]
YJL128C  PBS2; mitogen-activated protein kinase kinase PBS2 [KO:K11227] [EC:2.7.12.2]
YLR113W  HOG1; mitogen-activated protein kinase HOG1 [KO:K04441] [EC:2.7.11.24]
YIL035C  CKA1; casein kinase 2 catalytic subunit CKA1 [KO:K03097] [EC:2.7.11.1]
YOR061W  CKA2; casein kinase 2 catalytic subunit CKA2 [KO:K03097] [EC:2.7.11.1]
YGL019W  CKB1; casein kinase 2 regulatory subunit CKB1 [KO:K03115]
YOR039W  CKB2; casein kinase 2 regulatory subunit CKB2 [KO:K03115]
YIL065C  FIS1; Fis1p [KO:K17969]
YLL001W  DNM1; dynamin-related GTPase DNM1 [KO:K17065] [EC:3.6.5.5]
YPR049C  ATG11; autophagy protein ATG11 [KO:K08330]
YGL219C  MDM34; ERMES complex subunit MDM34 [KO:K17775]
YAL010C  MDM10; Mdm10p [KO:K17774]
YOL009C  MDM12; ERMES complex subunit MDM12 [KO:K17765]
YLL006W  MMM1; ERMES complex subunit MMM1 [KO:K17764]
YBL078C  ATG8; ubiquitin-like protein ATG8 [KO:K08341]
YGL180W  ATG1; serine/threonine protein kinase ATG1 [KO:K08269] [EC:2.7.11.1]
YLR356W  ATG33; Atg33p [KO:K19717]
YCR079W  PTC6; type 2C protein phosphatase PTC6 [KO:K19708] [EC:3.1.3.16 3.1.3.43]
YDR208W  MSS4; 1-phosphatidylinositol-4-phosphate 5-kinase [KO:K00889] [EC:2.7.1.68]
YIL098C  FMC1; Fmc1p [KO:K18191]
YOR330C  MIP1; DNA-directed DNA polymerase gamma MIP1 [KO:K02332] [EC:2.7.7.7]
YOL027C  MDM38; ribosome-binding protein MDM38 [KO:K17800]
YER151C  UBP3; mRNA-binding ubiquitin-specific protease UBP3 [KO:K11841] [EC:3.4.19.12]
YNR051C  BRE5; Bre5p [KO:K19718]
Compound
D00753  Sirolimus (JAN/USAN/INN)
Reference
  Authors
Kanki T, Furukawa K, Yamashita S
  Title
Mitophagy in yeast: Molecular mechanisms and physiological role.
  Journal
Biochim Biophys Acta 1853:2756-65 (2015)
DOI:10.1016/j.bbamcr.2015.01.005
Reference
  Authors
Muller M, Lu K, Reichert AS
  Title
Mitophagy and mitochondrial dynamics in Saccharomyces cerevisiae.
  Journal
Biochim Biophys Acta 1853:2766-74 (2015)
DOI:10.1016/j.bbamcr.2015.02.024
Reference
  Authors
Okamoto K, Kondo-Okamoto N, Ohsumi Y
  Title
Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy.
  Journal
Dev Cell 17:87-97 (2009)
DOI:10.1016/j.devcel.2009.06.013
Reference
  Authors
Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ
  Title
Atg32 is a mitochondrial protein that confers selectivity during mitophagy.
  Journal
Dev Cell 17:98-109 (2009)
DOI:10.1016/j.devcel.2009.06.014
Reference
  Authors
Mao K, Wang K, Zhao M, Xu T, Klionsky DJ
  Title
Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae.
  Journal
J Cell Biol 193:755-67 (2011)
DOI:10.1083/jcb.201102092
Reference
  Authors
Aoki Y, Kanki T, Hirota Y, Kurihara Y, Saigusa T, Uchiumi T, Kang D
  Title
Phosphorylation of Serine 114 on Atg32 mediates mitophagy.
  Journal
Mol Biol Cell 22:3206-17 (2011)
DOI:10.1091/mbc.E11-02-0145
Reference
  Authors
Kanki T, Kurihara Y, Jin X, Goda T, Ono Y, Aihara M, Hirota Y, Saigusa T, Aoki Y, Uchiumi T, Kang D
  Title
Casein kinase 2 is essential for mitophagy.
  Journal
EMBO Rep 14:788-94 (2013)
DOI:10.1038/embor.2013.114
Reference
  Authors
Kondo-Okamoto N, Noda NN, Suzuki SW, Nakatogawa H, Takahashi I, Matsunami M, Hashimoto A, Inagaki F, Ohsumi Y, Okamoto K
  Title
Autophagy-related protein 32 acts as autophagic degron and directly initiates mitophagy.
  Journal
J Biol Chem 287:10631-8 (2012)
DOI:10.1074/jbc.M111.299917
Reference
  Authors
Mao K, Wang K, Liu X, Klionsky DJ
  Title
The scaffold protein Atg11 recruits fission machinery to drive selective mitochondria degradation by autophagy.
  Journal
Dev Cell 26:9-18 (2013)
DOI:10.1016/j.devcel.2013.05.024
Reference
  Authors
Wang K, Jin M, Liu X, Klionsky DJ
  Title
Proteolytic processing of Atg32 by the mitochondrial i-AAA protease Yme1 regulates mitophagy.
  Journal
Autophagy 9:1828-36 (2013)
DOI:10.4161/auto.26281
Reference
  Authors
Tal R, Winter G, Ecker N, Klionsky DJ, Abeliovich H
  Title
Aup1p, a yeast mitochondrial protein phosphatase homolog, is required for efficient stationary phase mitophagy and cell survival.
  Journal
J Biol Chem 282:5617-24 (2007)
DOI:10.1074/jbc.M605940200
Reference
  Authors
Kanki T, Wang K, Baba M, Bartholomew CR, Lynch-Day MA, Du Z, Geng J, Mao K, Yang Z, Yen WL, Klionsky DJ
  Title
A genomic screen for yeast mutants defective in selective mitochondria autophagy.
  Journal
Mol Biol Cell 20:4730-8 (2009)
DOI:10.1091/mbc.E09-03-0225
Reference
  Authors
Wang K, Yang Z, Liu X, Mao K, Nair U, Klionsky DJ
  Title
Phosphatidylinositol 4-kinases are required for autophagic membrane trafficking.
  Journal
J Biol Chem 287:37964-72 (2012)
DOI:10.1074/jbc.M112.371591
Reference
  Authors
Priault M, Salin B, Schaeffer J, Vallette FM, di Rago JP, Martinou JC
  Title
Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast.
  Journal
Cell Death Differ 12:1613-21 (2005)
DOI:10.1038/sj.cdd.4401697
Reference
  Authors
Nowikovsky K, Reipert S, Devenish RJ, Schweyen RJ
  Title
Mdm38 protein depletion causes loss of mitochondrial K+/H+ exchange activity, osmotic swelling and mitophagy.
  Journal
Cell Death Differ 14:1647-56 (2007)
DOI:10.1038/sj.cdd.4402167
Reference
  Authors
Zhang Y, Qi H, Taylor R, Xu W, Liu LF, Jin S
  Title
The role of autophagy in mitochondria maintenance: characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains.
  Journal
Autophagy 3:337-46 (2007)
DOI:10.4161/auto.4127
Reference
  Authors
Muller M, Kotter P, Behrendt C, Walter E, Scheckhuber CQ, Entian KD, Reichert AS
  Title
Synthetic quantitative array technology identifies the Ubp3-Bre5 deubiquitinase complex as a negative regulator of mitophagy.
  Journal
Cell Rep 10:1215-25 (2015)
DOI:10.1016/j.celrep.2015.01.044
Related
pathway
sce04011  MAPK signaling pathway - yeast
sce04138  Autophagy - yeast
KO pathway
ko04139   
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