Distinct Roles of Mitochondrial HIGD1A and HIGD2A in Respiratory Complex and Supercomplex Biogenesis. Cell Rep 2020 May 05;31(5):107607
Date
05/07/2020Pubmed ID
32375044DOI
10.1016/j.celrep.2020.107607Scopus ID
2-s2.0-85084125359 (requires institutional sign-in at Scopus site) 63 CitationsAbstract
The mitochondrial respiratory chain enzymes are organized as individual complexes and supercomplexes, whose biogenesis remains to be fully understood. To disclose the role of the human Hypoxia Inducible Gene Domain family proteins HIGD1A and HIGD2A in these processes, we generate and characterize HIGD-knockout (KO) cell lines. We show that HIGD2A controls and coordinates the modular assembly of isolated and supercomplexed complex IV (CIV) by acting on the COX3 assembly module. In contrast, HIGD1A regulates CIII and CIII-containing supercomplex biogenesis by supporting the incorporation of UQCRFS1. HIGD1A also clusters with COX4-1 and COX5A CIV subunits and, when overexpressed, suppresses the CIV biogenesis defect of HIGD2A-KO cells. We conclude that HIGD1A and HIGD2A have both independent and overlapping functions in the biogenesis of respiratory complexes and supercomplexes. Our data illuminate the existence of multiple pathways to assemble these structures by dynamic HIGD-mediated CIV biogenesis, potentially to adapt to changing environmental and nutritional conditions.
Author List
Timón-Gómez A, Garlich J, Stuart RA, Ugalde C, Barrientos AAuthor
Rosemary Stuart PhD Professor in the Biology department at Marquette UniversityMESH terms used to index this publication - Major topics in bold
Electron Transport Complex IVHumans
Intracellular Signaling Peptides and Proteins
Iron-Sulfur Proteins
Mitochondria
Mitochondrial Membranes
Mitochondrial Proteins
