KEGG   PATHWAY: svg04137
Entry
svg04137                    Pathway                                
Name
Mitophagy - animal - Sturnus vulgaris (common starling)
Description
Mitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process called reactive oxidative species (ROS) lead to mitochondrial dysfunction. If the damage is too excessive to be repaired, such mitochondria are selectively recognized and targeted for degradation by a specific mode of autophagy, termed mitophagy. The loss of the mitochondrial membrane potential can induce mitophagy, involving the kinase PINK1 and the E3 ligase Parkin. PINK1 serves as the sensor for the mitochondrial depolarization and recruits Parkin, followed by ubiquitin-dependent recruitment of mitophagy receptors. There are also several PINK1/Parkin-independent mitophagy pathways, in which a group of LIR-containing receptors are required in response to different stimuli. Mitophagy contributes to the maintenance of a healthy mitochondrial network and the prevention of programmed cell death.
Class
Cellular Processes; Transport and catabolism
Pathway map
svg04137  Mitophagy - animal
svg04137

Other DBs
GO: 0000422
Organism
Sturnus vulgaris (common starling) [GN:svg]
Gene
106856490  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
106856437  PINK1; serine/threonine-protein kinase PINK1, mitochondrial [KO:K05688] [EC:2.7.11.1]
106864727  TOMM7; mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
106862336  TOMM40L; mitochondrial import receptor subunit TOM40B [KO:K11518]
106852352  TOMM20; mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
106858839  TOMM70A; mitochondrial import receptor subunit TOM70 [KO:K17768]
106852963  PARK2; E3 ubiquitin-protein ligase parkin [KO:K04556] [EC:2.3.2.31]
106852632  MARCH5; E3 ubiquitin-protein ligase MARCH5 isoform X1 [KO:K10660] [EC:2.3.2.27]
106855986  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
106849829  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
106856954  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
106855851  AMFR; E3 ubiquitin-protein ligase AMFR [KO:K10636] [EC:2.3.2.36]
106850346  mitochondrial ubiquitin ligase activator of nfkb 1-A-like isoform X1 [KO:K15688] [EC:2.3.2.27]
106856458  MUL1; mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
106856877  SIAH1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
106861060  ARIH1; E3 ubiquitin-protein ligase ARIH1 [KO:K11968] [EC:2.3.2.31]
106850311  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
106856432  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
106854334  RHOT1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
106860608  RHOT2; mitochondrial Rho GTPase 2 isoform X1 [KO:K07871] [EC:3.6.5.-]
106859759  UBA52; ubiquitin-60S ribosomal protein L40 [KO:K02927]
106865208  RPS27A; ubiquitin-40S ribosomal protein S27a [KO:K02977]
106853309  UBB; polyubiquitin-B [KO:K04551]
106864421  TAX1BP1; tax1-binding protein 1 isoform X1 [KO:K21347]
106859588  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
106857190  OPTN; optineurin isoform X1 [KO:K19946]
106858681  NBR1; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
106860662  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
106864281  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
106856284  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
106861274  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
106858494  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
106859198  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A isoform X1 [KO:K10435]
106852060  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
106858650  BECN1; beclin-1 [KO:K08334]
106860057  USP8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
106862095  USP15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
106852456  USP30; ubiquitin carboxyl-terminal hydrolase 30 [KO:K11851] [EC:3.4.19.12]
106861623  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
106864765  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial [KO:K15637] [EC:3.1.3.16]
106860920  CSNK2A2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
106861620  CSNK2A1; casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
106857764  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
106852388  ULK1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
106853527  FUNDC1; FUN14 domain-containing protein 1 [KO:K17986]
106861942  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
106858482  BNIP3L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like [KO:K15465]
106849431  BCL2L13; bcl-2-like protein 13 [KO:K15485]
106859758  FKBP8; peptidyl-prolyl cis-trans isomerase FKBP8 isoform X1 [KO:K09574] [EC:5.2.1.8]
106855977  SAMM50; sorting and assembly machinery component 50 homolog [KO:K07277]
106857864  PHB2; prohibitin-2 [KO:K17081]
106858163  NLRX1; NLR family member X1 [KO:K12653]
106855499  MTX2; metaxin-2 isoform X1 [KO:K17776]
106856224  MTX3; metaxin-3 isoform X1 [KO:K17776]
106861132  MTX1; metaxin-1 [KO:K17776]
106853142  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
106849054  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
106858572  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
106852620  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
106859575  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
106855713  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
106849741  JUN; transcription factor AP-1 [KO:K04448]
106863554  RELA; transcription factor p65 [KO:K04735]
106851547  HRAS; GTPase HRas [KO:K02833]
106860955  KRAS; GTPase KRas isoform X1 [KO:K07827]
106851063  NRAS; GTPase NRas [KO:K07828]
106850425  MRAS; ras-related protein M-Ras [KO:K07831]
106853206  RRAS2; ras-related protein R-Ras2 [KO:K07830]
106853078  E2F1; transcription factor E2F1 [KO:K17454]
106850215  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
106863620  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
106860163  FOXO3; forkhead box protein O3 [KO:K09408]
106854899  CITED2; cbp/p300-interacting transactivator 2 [KO:K21361]
106851483  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
106851016  TFEB; transcription factor EB [KO:K15590]
106853383  RABGEF1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
106857354  RAB5A; ras-related protein Rab-5A [KO:K07887]
106858645  RAB5C; ras-related protein Rab-5C [KO:K07889]
106864112  MON1B; vacuolar fusion protein MON1 homolog B [KO:K20195]
106849240  MON1A; vacuolar fusion protein MON1 homolog A [KO:K20195]
106849167  CCZ1; vacuolar fusion protein CCZ1 homolog [KO:K27045]
106861835  RAB7A; ras-related protein Rab-7a [KO:K07897]
106850997  RAB7B; ras-related protein Rab-7b [KO:K07898]
106855044  TBC1D15; TBC1 domain family member 15 isoform X1 [KO:K20168]
106860299  ATG9A; autophagy-related protein 9A [KO:K17907]
106861780  ATG9B; autophagy-related protein 9B [KO:K17907]
106860803  OPA1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
106859057  VCP; transitional endoplasmic reticulum ATPase [KO:K13525]
Compound
C00035  GDP
C00044  GTP
Reference
  Authors
Pickrell AM, Youle RJ
  Title
The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
  Journal
Neuron 85:257-73 (2015)
DOI:10.1016/j.neuron.2014.12.007
Reference
  Authors
Durcan TM, Fon EA
  Title
The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
  Journal
Genes Dev 29:989-99 (2015)
DOI:10.1101/gad.262758.115
Reference
  Authors
Shirihai OS, Song M, Dorn GW 2nd
  Title
How mitochondrial dynamism orchestrates mitophagy.
  Journal
Circ Res 116:1835-49 (2015)
DOI:10.1161/CIRCRESAHA.116.306374
Reference
  Authors
Hamacher-Brady A, Brady NR
  Title
Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
  Journal
Cell Mol Life Sci 73:775-95 (2016)
DOI:10.1007/s00018-015-2087-8
Reference
  Authors
Yamano K, Matsuda N, Tanaka K
  Title
The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation.
  Journal
EMBO Rep 17:300-16 (2016)
DOI:10.15252/embr.201541486
Reference
  Authors
Yamaguchi O, Murakawa T, Nishida K, Otsu K
  Title
Receptor-mediated mitophagy.
  Journal
J Mol Cell Cardiol 95:50-6 (2016)
DOI:10.1016/j.yjmcc.2016.03.010
Reference
  Authors
Roberts RF, Tang MY, Fon EA, Durcan TM
  Title
Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles.
  Journal
Int J Biochem Cell Biol 79:427-436 (2016)
DOI:10.1016/j.biocel.2016.07.020
Reference
  Authors
Arena G, Valente EM
  Title
PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease.
  Journal
J Pathol 241:251-263 (2017)
DOI:10.1002/path.4815
Related
pathway
svg04140  Autophagy - animal
svg04210  Apoptosis
KO pathway
ko04137   
LinkDB

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