Table 1.

Known female germ cell phenotypes for autophagy/mitophagy genes.

Process/proteina		Species	Mouse fertilityb	Fly fertility	Mouse viabilityb
Turning on the pathway
mTORC1	Many	H/M/D	Reduced fertility1	Tor RNAi-sterile
TFEB	Transcription factor	H/M/D	ND	ND	Lethal2
RHEB	Small GTP-binding proteins, Ras superfamily	H/M/D	Fertile3	Female sterile (viable mutation)4	Embryonic lethal5
Initiation of autophagosome biogenesis
ULK complex
ULK1, 2	Ser/Thr kinase catalytic subunit of ULK	H/M/D	ND	(Atg1) Female sterile (RNAi)6, 7	DKO for ULK1/2 Embryonic lethal8
ATG13	Regulatory subunit of ULK	H/M/D	ND	Fertile	lethal9
ATG101	Subunit of ULK	H/M/D	ND	ND	ND
FIP200	Subunit of ULK	H/M/D	ND	(Atg17) ND	Embryonic lethal10
AMPK (α, β, γ)	Ser/Thr kinase	H/M/D	(α1) Decreased litter size, abnormal mitochondrial physiology11	Female sterile (RNAi)12	Viable (α1, 2)13 Viable (γ)13
ATG9	Transmembrane protein	H/M/D	ND	Sterile (null mutant)14	Lethal neonatal15
VPS34-I
VPS34	Class III PI-3 kinase subunit of VPS34-1	H/M/D	ND	ND	Embryonic lethal16
VPS15	Subunit of VPS34-1	H/M/D	ND	Semi-sterile (RNAi)12	Embryonic lethal17
BECN1	Regulatory subunit of VPS34-1	H/M/D	Infertile18	(Atg6) ND	Embryonic lethal19
ATG14L	Subunit of VPS34-1	H/M/D	ND	ND	ND
AMBRA	Regulator of BECN1	H/M	ND	–	Lethal20
MAPKAP2,3	Ser/Thr kinases	H/M/D	Fertile21	Semi-sterile (RNAi)12	Viable21
DFCP1	PI(3)P-binding protein	H/M	ND	–	Viable22
WIPI1,2	PI(3)P-binding protein	H/M/D	ND	ND	ND
Building the autophagosome
Lipidation complex
ATG12	Part of ubiquitin ligation-like (E3) complex	H/M/D	ND	ND	Lethal neonatal23
ATG3	Part of ubiquitin ligation-like (E3) complex	H/M/D	ND	ND	Lethal neonatal24
ATG5	Part of ubiquitin ligation-like (E3) complex	H/M/D	Oocyte development normal, early embryonic lethal25	Fertile	Lethal neonatal26
ATG7	Part of ubiquitin ligation-like (E3) complex	H/M/D	Subfertile27	ND	Lethal neonatal28
ATG16L	Part of ubiquitin ligation-like (E3) complex	H/M/D	ND	Fertile	Lethal neonatal29
LC3A, B, C	Ubiquitin-like proteins	H/M/D	LC3B Fertile (JAX)	(Atg8a, Atg8b) ND	LC3B viable30
GABARAP, L1, L2	Ubiquitin-like proteins	H/M/D	ND	(Atg8a, Atg8b) ND	GABARAP viable31 L1 viable32 L2 lethal33
ATG2b	Phospholipid binding/transfer protein	H/M/D	ND	ND	Viable (IMPC)
VMP1	ER-resident protein	H/M/D	ND	ND	Lethal34
Fusing autophagosome with lysosome
STX17	SNARE protein	H/M/D	ND	(Syx17) fertile	ND
RAB7	Small GTP-binding proteins, Ras superfamily	H/M/D	ND	ND	s
EPG5	RAB7 effector protein	H/M/D	ND	ND	Viable, reduced survival 36
HOPS (VPS11, VPS16, VPS18, VPS33A)	Tethering complex	H/M/D	ND	(Car) ND (Cm) ND	VPS33A, 16, viable, impaired motor function37
PLEKHM1	HOPS-interacting protein	H/M/D	Fertile 38	ND	Viable38
Ubiquitin-mediated mitophagy
PINK1	Kinase	H/M/D	Fertile (JAX)	Sterile39	Viable40
OPTN	Mitophagy receptor	H/M/D	Fertile41	(Nemo) Semi-sterile 7	Viable41
PARK2	E3 ubiquitin ligase	H/M/D	Fertile42	Semi-sterile 12, 43	Viable42
P62 (SQSTM1)	Mitophagy receptor	H/M/D	ND	(Ref(2)P) Fertile	Viable44
TAX1BP1	Mitophagy receptor	H/M	ND	–	Viable45
NDP52	Mitophagy receptor	H/M	ND	–	Viable (IMPC)
NBR1	Mitophagy receptor	H/M	ND	–	Viable (IMPC)
OMM mitophagy receptors				–
BNIP3	Mitophagy receptor	H/M	Fertile46	–	Viable46
BNIP3L (NIX)	Mitophagy receptor	H/M	ND	–	Viable47
BCL2L13	Mitophagy receptor	H/M	Reduced fertility 48	–	Viable48
FUNDC1	Mitophagy receptor	H/M	Fertile49	–	Male lethal (IMPC)
Lysosomal
LAMP1		H/M/D	Fertile50	ND	Viable50

^aProtein functions listed are those that are related to mitophagy/autophagy. Other important cellular functions may have been ascribed to individual proteins. ^bFertility and viability were assessed from literature, Jackson Laboratory (JAX) breeding information, Mouse Genome Informatics (MGI), and the International Mouse Phenotyping Consortium (IMPC). Fertility information may indicate that homozygotes can breed or produce offspring however this does not necessarily mean oocyte development in normal. In some cases, while a strain is viable it may have abnormalities and it is not clear if it is fertile (ND). Viability was assessed for available information on whole body knockout. Phenotypic description of whole body knockouts may not be included in the original study generating the knockout strain. DKO, double knockout; H/M/D, human/mouse/Drosophila; ND, no data; OMM, outer mitochondrial membrane. ¹Guo and Yu (2019); ²Steingrimsson et al. (1998); ³Baker et al. (2014); ⁴Stocker et al. (2003); ⁵Goorden et al. (2011); ⁶Lieber et al. (2019); ⁷Kuhn et al. (2015); ⁸Cheong et al. (2014); ⁹Kaizuka and Mizushima (2016); ¹⁰Gan et al. (2006); ¹¹Bertoldo et al. (2015); ¹²Sopko et al. (2014); ¹³Jorgensen et al. (2004); ¹⁴Wen et al. (2017); ¹⁵Saitoh et al. (2009); ¹⁶Zhou et al. (2011); ¹⁷Nemazanyy et al. (2013); ¹⁸Gawriluk et al. (2011); ¹⁹Yue et al. (2003); ²⁰Fimia et al. (2007); ²¹Ronkina et al. (2007); ²²Zhong et al. (2020); ²³Malhotra et al. (2015); ²⁴Sou et al. (2008); ²⁵Tsukamoto et al. (2008b); ²⁶Kuma et al. (2004); ²⁷Song et al. (2015); ²⁸Komatsu et al. (2005); ²⁹Saitoh et al. (2008); ³⁰Cann et al. (2008); ³¹O’Sullivan et al. (2005); ³²Sasai et al. (2017); ³³Skarnes et al. (2011); ³⁴Morishita et al. (2019); ³⁵Kawamura et al. (2012); ³⁶Zhao et al. (2013); ³⁷Zhen and Li (2015); ³⁸Fujiwara et al. (2016); ³⁹Politi et al. (2014); ⁴⁰Kitada et al. (2007); ⁴¹Slowicka et al. (2016); ⁴²Itier et al. (2003); ⁴³Cox and Spradling (2009); ⁴⁴Wada et al. (2006); ⁴⁵Iha et al. (2008); ⁴⁶Diwan et al. (2007); ⁴⁷Yuan et al. (2017); ⁴⁸D’Alonzo and Hong (2017); ⁴⁹Zhang et al. (2016); ⁵⁰Andrejewski et al. (1999).