Autophagic elimination of ribosomes during spermiogenesis provides energy for flagellar motility

Yuqing Lei; Xueguang Zhang; Qingjia Xu; Shiyan Liu; Chunxia Li; Hui Jiang; Haocheng Lin; Eryan Kong; Jiaming Liu; Shiqian Qi; Huihui Li; Wenming Xu; Kefeng Lu

doi:10.1016/j.devcel.2021.07.015

Autophagic elimination of ribosomes during spermiogenesis provides energy for flagellar motility

Dev Cell. 2021 Aug 23;56(16):2313-2328.e7. doi: 10.1016/j.devcel.2021.07.015.

Authors

Yuqing Lei¹, Xueguang Zhang², Qingjia Xu³, Shiyan Liu³, Chunxia Li³, Hui Jiang⁴, Haocheng Lin⁴, Eryan Kong⁵, Jiaming Liu⁶, Shiqian Qi⁶, Huihui Li⁷, Wenming Xu⁸, Kefeng Lu⁹

Affiliations

¹ Department of Pathology, West China Second University Hospital, State Key Laboratory of Biotherapy, and Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Sichuan University, Chengdu 610041, China.
² Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
³ Department of Neurology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
⁴ Department of Urology, Peking University Third Hospital, Beijing 100191, China; Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing 100191, China.
⁵ Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang 453003, China.
⁶ Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
⁷ Department of Pathology, West China Second University Hospital, State Key Laboratory of Biotherapy, and Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Sichuan University, Chengdu 610041, China. Electronic address: lihuihui@scu.edu.cn.
⁸ Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China. Electronic address: xuwenming@scu.edu.cn.
⁹ Department of Neurology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: lukf@scu.edu.cn.

PMID: 34428398
DOI: 10.1016/j.devcel.2021.07.015

Abstract

How autophagy initiation is regulated and what the functional significance of this regulation is are unknown. Here, we characterized the role of yeast Vac8 in autophagy initiation through recruitment of PIK3C3-C1 to the phagophore assembly site (PAS). This recruitment is dependent on the palmitoylation of Vac8 and on its middle ARM domains for binding PIK3C3-C1. Vac8-mediated anchoring of PIK3C3-C1 promotes PtdIns3P generation at the PAS and recruitment of the PtdIns3P binding protein Atg18-Atg2. The mouse homolog of Vac8, ARMC3, is conserved and functions in autophagy in mouse testes. Mice lacking ARMC3 have normal viability but show complete male infertility. Proteomic analysis indicated that the autophagic degradation of cytosolic ribosomes was blocked in ARMC3-deficient spermatids, which caused low energy levels of mitochondria and motionless flagella. These studies uncovered a function of Vac8/ARMC3 in PtdIns3-kinase anchoring at the PAS and its physical significance in mammalian spermatogenesis with a germ tissue-specific autophagic function.

Keywords: ARM; ARMC3; PIK3C3-C1; PtdIns3P; Vac8; autophagy; flagellum motility; mitochondria; palmitoylation; ribosome; spermatogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Autophagosomes / metabolism
Autophagy*
Cells, Cultured
Class III Phosphatidylinositol 3-Kinases / metabolism
HEK293 Cells
Humans
Male
Mice
Mice, Inbred C57BL
Ribosomes / metabolism*
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Sperm Motility
Sperm Tail / metabolism*
Sperm Tail / physiology
Spermatogenesis*
Vesicular Transport Proteins / genetics
Vesicular Transport Proteins / metabolism

Substances

Saccharomyces cerevisiae Proteins
VAC8 protein, S cerevisiae
Vesicular Transport Proteins
Class III Phosphatidylinositol 3-Kinases
PIK3C3 protein, mouse