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

Liang Wang; Ziyi Yan; Helena Vihinen; Ove Eriksson; Weihuan Wang; Rabah Soliymani; Yao Lu; Yaxin Xue; Eija Jokitalo; Jing Li; Hongxia Zhao

doi:10.1083/jcb.201806191

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.

Authors

Liang Wang¹, Ziyi Yan¹, Helena Vihinen¹, Ove Eriksson², Weihuan Wang^{1

3}, Rabah Soliymani⁴, Yao Lu¹, Yaxin Xue¹, Eija Jokitalo¹, Jing Li³, Hongxia Zhao⁵

Affiliations

¹ Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
² Biochemistry/Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
³ College of Life Sciences, Northwest A&F University, Yangling, China.
⁴ Meilahti Clinical Proteomics Core Facility, HiLIFE, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁵ Institute of Biotechnology, University of Helsinki, Helsinki, Finland [email protected].

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