Mitochondrial Proteins Containing Coiled-Coil-Helix-Coiled-Coil-Helix (CHCH) Domains in Health and Disease
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Updated: Mar 27, 2026

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights
Published on: June 16, 2023
Nazanine Modjtahedi1, Kostas Tokatlidis2, Philippe Dessen3
1Institut National de la Santé et de la Recherche Médicale, U1030, Villejuif, France; Gustave Roussy Cancer Campus, Villejuif, France; Faculty of Medicine, Université Paris-Saclay, Kremlin-Bicêtre, France.
Abstract:
Members of the coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing protein family that carry (CX9C) type motifs are imported into the mitochondrion with the help of the disulfide relay-dependent MIA import pathway. These evolutionarily conserved proteins are emerging as new cellular factors that control mitochondrial respiration, redox regulation, lipid homeostasis, and membrane ultrastructure and dynamics. We discuss recent insights on the activity of known (CX9C) motif-carrying proteins in mammals and review current data implicating the Mia40/CHCHD4 import machinery in the regulation of their mitochondrial import. Recent findings and the identification of disease-associated mutations in specific (CX9C) motif-carrying proteins have highlighted members of this family of proteins as potential therapeutic targets in a variety of human disorders.
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