title: FSH protects mouse granulosa cells from oxidative damage by repressing mitophagy.
abstract: Oxidative stress has been implicated in triggering granulosa cell (GC) death during follicular atresia. Recent studies suggested that follicle-stimulating hormone (FSH) has a pivotal role in protecting GCs from oxidative injury, although the exact mechanism remains largely unknown. Here, we report that FSH promotes GC survival by inhibiting oxidative stress-induced mitophagy. The loss of GC viability caused by oxidative stress was significantly reduced after FSH treatment, which was correlated with impaired activation of mitophagy upon oxidative stress. Compared with FSH treatment, blocking mitophagy displayed approximate preventive effect on oxidative stress-induced GC death, but FSH did not further restore viability of cells pretreated with mitophagy inhibitor. Importantly, FSH suppressed the induction of serine/threonine kinase PINK1 during oxidative stress. This inhibited the mitochondrial translocation of the E3 ligase Parkin, which is required for the subsequent clearance of mitochondria, and ultimately cell death via mitophagy. In addition, knocking down PINK1 using RNAi confirmed the role of the FSH-PINK1-Parkin-mitophagy pathway in regulating GC survival under oxidative conditions. These findings introduce a novel physiological function of FSH in protecting GCs against oxidative damage by targeting PINK1-Parkin-mediated mitophagy.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Guan
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Shao-Chen
authors.initials: SC
authors.lastname: Sun
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D063306:Mitophagy / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D011494:Protein Kinases / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D005640:Follicle Stimulating Hormone; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein