title: MYBL2 guides autophagy suppressor VDAC2 in the developing ovary to inhibit autophagy through a complex of VDAC2-BECN1-BCL2L1 in mammals.
abstract: Oogenesis is essential for female gamete production in mammals. The total number of ovarian follicles is determined early in life and production of ovarian oocytes is thought to stop during the lifetime. However, the molecular mechanisms underling oogenesis, particularly autophagy regulation in the ovary, remain largely unknown. Here, we reveal an important MYBL2-VDAC2-BECN1-BCL2L1 pathway linking autophagy suppression in the developing ovary. The transcription factors GATA1 and MYBL2 can bind to and activate the Vdac2 promoter. MYBL2 regulates the spatiotemporal expression of VDAC2 in the developing ovary. Strikingly, in the VDAC2 transgenic pigs (Sus scrofa/Ss), VDAC2 exerts its function by inhibiting autophagy in the ovary. In contrast, Vdac2 knockout promotes autophagy. Moreover, VDAC2-mediated autophagy suppression is dependent on its interactions with both BECN1 and BCL2L1 to stabilize the BECN1 and BCL2L1 complex, suggesting VDAC2 as an autophagy suppressor in the pathway. Our findings provide a functional connection among the VDAC2, MYBL2, the BECN1-BCL2L1 pathway and autophagy suppression in the developing ovary, which is implicated in improving female fecundity.
authors.affiliation: a Department of Genetics; College of Life Sciences; Wuhan University ; Wuhan , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yuan
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Sheng
authors.forename: Xiazhou
authors.initials: X
authors.lastname: Fu
authors.forename: Hanhua
authors.initials: H
authors.lastname: Cheng
authors.forename: Rongjia
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D004252:DNA Mutational Analysis; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D050982:GATA1 Transcription Factor / Q000378:metabolism; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034421:Sus scrofa; D015534:Trans-Activators / Q000378:metabolism*; D050996:Voltage-Dependent Anion Channel 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D050982:GATA1 Transcription Factor; D015534:Trans-Activators; D050996:Voltage-Dependent Anion Channel 2; D051020:bcl-X Protein
keywords: ATG12, autophagy-related 12; ATG16L1, autophagy-related 16-like 1; ATG5, autophagy-related 5; BAK, BCL2-antagonist/killer 1; BCL2, B-cell CLL/lymphoma 2; BCL2L1, BCL2-like 1; BECN1, Beclin 1, autophagy related; Beclin1; CDS, coding DNA sequence; Dpp, days postpartum; GATA1, GATA binding protein 1 (globin transcription factor 1); GATA2, GATA binding protein 2; LC3B, microtubule-associated protein 1 light chain 3 beta; MBS, MYBL2 binding site; MYBL2; MYBL2, v-myb avian myeloblastosis viral oncogene homolog-like 2; SP1, Sp1 transcription factor; VDAC, voltage-dependent anion channel; VDAC2; ovary; reproduction; transcription regulation; wt, wild type