KEGG   PATHWAY: mmf04137
Entry
mmf04137                    Pathway                                
Name
Mitophagy - animal - Molossus molossus (Pallas's mastiff bat)
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
mmf04137  Mitophagy - animal
mmf04137

Other DBs
GO: 0000422
Organism
Molossus molossus (Pallas's mastiff bat) [GN:mmf]
Gene
118615122  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118615259  FKBP8; peptidyl-prolyl cis-trans isomerase FKBP8 isoform X1 [KO:K09574] [EC:5.2.1.8]
118615289  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
118615881  CCZ1; vacuolar fusion protein CCZ1 homolog isoform X1 [KO:K27045]
118616880  OPA1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
118616884  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
118617343  [KO:K02927]
118617433  TOMM70; mitochondrial import receptor subunit TOM70 [KO:K17768]
118617547  [KO:K08341]
118618120  RAB7A; ras-related protein Rab-7a isoform X1 [KO:K07897]
118618234  BCL2L1; bcl-2-like protein 1 [KO:K04570]
118618720  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
118618748  E2F1; transcription factor E2F1 [KO:K17454]
118618750  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
118619034  CSNK2A1; casein kinase II subunit alpha isoform X1 [KO:K03097] [EC:2.7.11.1]
118619537  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
118620068  ATG9B; autophagy-related protein 9B [KO:K17907]
118620069  TAX1BP1; tax1-binding protein 1 isoform X1 [KO:K21347]
118620128  TOMM7; mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
118620791  ARIH1; E3 ubiquitin-protein ligase ARIH1 isoform X1 [KO:K11968] [EC:2.3.2.31]
118620981  TFEB; transcription factor EB [KO:K15590]
118621147  [KO:K10660] [EC:2.3.2.27]
118621680  CSNK2B; casein kinase II subunit beta [KO:K03115]
118621858  FOXO3; forkhead box protein O3 [KO:K09408]
118621965  PRKN; E3 ubiquitin-protein ligase parkin [KO:K04556] [EC:2.3.2.31]
118622010  CITED2; cbp/p300-interacting transactivator 2 [KO:K21361]
118623453  SP1; transcription factor Sp1 [KO:K04684]
118623463  TBC1D15; TBC1 domain family member 15 isoform X1 [KO:K20168]
118623493  RAB5B; ras-related protein Rab-5B [KO:K07888]
118623534  [KO:K02927]
118623538  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
118623566  [KO:K02977]
118623571  [KO:K02927]
118623987  USP15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
118624185  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
118624309  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
118624312  [KO:K03097] [EC:2.7.11.1]
118624450  SAMM50; sorting and assembly machinery component 50 homolog isoform X1 [KO:K07277]
118624565  PHB2; prohibitin-2 [KO:K17081]
118624619  KRAS; GTPase KRas isoform X1 [KO:K07827]
118624689  BCL2L13; bcl-2-like protein 13 isoform X1 [KO:K15485]
118625285  ATG9A; autophagy-related protein 9A isoform X1 [KO:K17907]
118625651  OPTN; optineurin isoform X1 [KO:K19946]
118625696  MTX2; metaxin-2 isoform X1 [KO:K17776]
118626081  PINK1; serine/threonine-protein kinase PINK1, mitochondrial isoform X1 [KO:K05688] [EC:2.7.11.1]
118626147  [KO:K02927]
118626149  [KO:K02927]
118626254  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
118626257  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
118626955  MUL1; mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
118627064  TOMM20L; TOMM20-like protein 1 [KO:K17770]
118627223  JUN; transcription factor AP-1 [KO:K04448]
118627687  [KO:K02927]
118627910  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
118627941  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
118628014  RRAS2; ras-related protein R-Ras2 [KO:K07830]
118628367  RELA; transcription factor p65 [KO:K04735]
118628767  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
118629495  [KO:K13525]
118629689  [KO:K17771]
118629846  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
118630702  RPS27A; ubiquitin-40S ribosomal protein S27a [KO:K02977]
118631170  [KO:K02927]
118631901  [KO:K02927]
118632382  MARCHF5; E3 ubiquitin-protein ligase MARCHF5 [KO:K10660] [EC:2.3.2.27]
118632456  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118632523  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
118632907  USP8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
118633308  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
118633604  MRAS; ras-related protein M-Ras [KO:K07831]
118633606  MON1A; LOW QUALITY PROTEIN: vacuolar fusion protein MON1 homolog A [KO:K20195]
118633803  NBR1; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
118633850  RHOT1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
118633915  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
118633999  [KO:K08341]
118634172  BECN1; beclin-1 [KO:K08334]
118634552  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
118634576  RAB5C; ras-related protein Rab-5C [KO:K07889]
118634664  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 [KO:K21348]
118635651  [KO:K04506] [EC:2.3.2.27]
118635681  HUWE1; E3 ubiquitin-protein ligase HUWE1 isoform X1 [KO:K10592] [EC:2.3.2.26]
118635984  [KO:K04506] [EC:2.3.2.27]
118636054  [KO:K04506] [EC:2.3.2.27]
118636057  [KO:K04506] [EC:2.3.2.27]
118636309  [KO:K04551]
118636390  TFE3; transcription factor E3 isoform X1 [KO:K09105]
118636643  FUNDC1; FUN14 domain-containing protein 1 [KO:K17986]
118637322  TOMM40L; mitochondrial import receptor subunit TOM40B [KO:K11518]
118637392  MTX1; metaxin-1 isoform X1 [KO:K17776]
118637563  RAB7B; ras-related protein Rab-7b [KO:K07898]
118637822  NRAS; GTPase NRas [KO:K07828]
118638270  TBC1D17; TBC1 domain family member 17 [KO:K19945]
118638422  AMFR; E3 ubiquitin-protein ligase AMFR [KO:K10636] [EC:2.3.2.36]
118638691  TOMM40; mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
118638755  CSNK2A2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
118638990  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
118639093  MON1B; vacuolar fusion protein MON1 homolog B [KO:K20195]
118639149  SIAH1; E3 ubiquitin-protein ligase SIAH1 [KO:K04506] [EC:2.3.2.27]
118639412  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
118639772  ULK1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
118639817  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
118639992  UBC; polyubiquitin-C [KO:K08770]
118640285  USP30; ubiquitin carboxyl-terminal hydrolase 30 [KO:K11851] [EC:3.4.19.12]
118640494  BECN2; beclin-2 [KO:K08334]
118640550  TOMM20; mitochondrial import receptor subunit TOM20 homolog isoform X1 [KO:K17770]
118640747  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
118641256  UBB; polyubiquitin-B [KO:K04551]
118641564  RABGEF1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
118641575  RHOT2; mitochondrial Rho GTPase 2 isoform X1 [KO:K07871] [EC:3.6.5.-]
118641674  MTX3; metaxin-3 isoform X1 [KO:K17776]
118641724  [KO:K02977]
118642157  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118642628  FIS1; mitochondrial fission 1 protein isoform X1 [KO:K17969]
118643162  HRAS; GTPase HRas isoform X1 [KO:K02833]
118643609  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
118643674  BNIP3L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like isoform X1 [KO:K15465]
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
mmf04140  Autophagy - animal
mmf04210  Apoptosis
KO pathway
ko04137   

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