FAM92A1 is a BAR domain protein required for mitochondrial ultrastructure and function

J Cell Biol. 2019 Jan 7;218(1):97-111. doi: 10.1083/jcb.201806191. Epub 2018 Nov 7.

Abstract

Mitochondrial function is closely linked to its dynamic membrane ultrastructure. The mitochondrial inner membrane (MIM) can form extensive membrane invaginations known as cristae, which contain the respiratory chain and ATP synthase for oxidative phosphorylation. The molecular mechanisms regulating mitochondrial ultrastructure remain poorly understood. The Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of diverse cellular processes related to membrane remodeling and dynamics. Whether BAR domain proteins are involved in sculpting membranes in specific submitochondrial compartments is largely unknown. In this study, we report FAM92A1 as a novel BAR domain protein localizes to the matrix side of the MIM. Loss of FAM92A1 caused a severe disruption to mitochondrial morphology and ultrastructure, impairing organelle bioenergetics. Furthermore, FAM92A1 displayed a membrane-remodeling activity in vitro, inducing a high degree of membrane curvature. Collectively, our findings uncover a role for a BAR domain protein as a critical organizer of the mitochondrial ultrastructure that is indispensable for mitochondrial function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Electron Transport Chain Complex Proteins / genetics*
  • Electron Transport Chain Complex Proteins / metabolism
  • Gene Expression Regulation
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Microscopy, Fluorescence
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Osteoblasts / metabolism
  • Osteoblasts / ultrastructure
  • Oxidative Phosphorylation
  • Protein Domains
  • Proteins / antagonists & inhibitors
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism

Substances

  • CIBAR1 protein, human
  • Electron Transport Chain Complex Proteins
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Proteins
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • TOMM20 protein, human
  • Green Fluorescent Proteins
  • Mitochondrial Proton-Translocating ATPases