Related Experiment Video

Updated: Oct 15, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

871

A conserved Vac8/ARMC3-PtdIns3K-CI cascade regulates autophagy initiation and functions in spermiogenesis by

Yuqing Lei1, Xueguang Zhang2, Qingjia Xu3

  • 1Department 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, China.

Autophagy
|October 27, 2021
PubMed

Insights

Autophagy initiation is clarified by the discovery of ARMC3 protein, crucial for recruiting key enzymes to build autophagosomes. This finding explains male infertility linked to ARMC3 deficiency in mice.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Macroautophagy/autophagy involves de novo autophagosome formation, requiring phosphatidylinositol-3-phosphate (PtdIns3P).
  • PtdIns3P is generated by class III phosphatidylinositol 3-kinase complex I (PtdIns3K-CI).
  • The precise mechanism initiating autophagy, specifically the recruitment of PtdIns3K-CI to the phagophore assembly site (PAS), remains largely unknown.

Purpose of the Study:

  • To elucidate the mechanism of autophagy initiation.
  • To identify the protein responsible for recruiting PtdIns3K-CI to the PAS.
  • To investigate the conserved function of ARMC3 in autophagy.

Main Methods:

  • Investigated the role of yeast Vac8 in recruiting PtdIns3K-CI to the PAS.
  • Identified mouse ARMC3 as the homolog of yeast Vac8.
  • Analyzed spermatids from Armc3-deleted mice.

Main Results:

  • Yeast Vac8 recruits PtdIns3K-CI to the PAS via N-terminal palmitoylation and ARM domain binding, initiating autophagosome formation.
  • Mouse ARMC3 conserves the autophagic function of Vac8.
  • Armc3 deletion in mice leads to blocked ribophagy, mitochondrial dysfunction, motionless flagella, and male infertility.

Conclusions:

  • ARMC3 plays a pivotal role in autophagy initiation by recruiting PtdIns3K-CI to the PAS.
  • ARMC3 exhibits conserved autophagic functions across species.
  • ARMC3 has a germ tissue-specific role in autophagy, essential for male fertility in complex eukaryotes.
Keywords:
ARMARMC3PtdIns3K-CIPtdIns3PVac8flagellamitochondriapalmitoylationribosomesperm

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