ArticleThe Journal of biological chemistry2011
ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
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Who cites it
191 citing papers in PubMed, 325 citations in OpenAlex.
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- Integrative structure determination of a human mitochondrial contact site and cristae organizing system (MICOS) sub-assembly.bioRxiv : the preprint server for biology · 2026Article
- Microglial CARD19 ameliorates post-stroke neuroinflammation by stabilizing mitochondrial cristae.Neural regeneration research · 2026Article
- MICOS and MIMAS, multifunctional assemblies linking mitochondrial biogenesis, architecture, and function.Protein science : a publication of the Protein Society · 2026Review
- Mitochondrial Dysfunction in Alzheimer's Disease and Mitochondria-Targeted Therapeutics.Cells · 2026Review
- Integrative immune subtyping of HNSCC reveals clinically relevant phenotypes and treatment-associated transitions.NPJ precision oncology · 2026Article
- Heart-Specific and Conditional Deletion of theCells · 2026Article
- The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.bioRxiv : the preprint server for biology · 2026Article
- Multi-Omic, Multi-Tissue Responses to Acute Exercise in Sedentary Adults: Findings from the Molecular Transducers of Physical Activity Consortium.bioRxiv : the preprint server for biology · 2026Article
- USP3 stabilizes MIC19 by deubiquitination under hypoxic stress and promotes the progression of non-small cell lung cancer.Acta pharmacologica Sinica · 2026Article
- Mitochondrial Fission Regulator 1-Like Protein Protects the Heart from Ischemia/Reperfusion Injury via Dual Mitochondrial Mechanisms.Research (Washington, D.C.) · 2026Article
- CHCHD3(MIC19): mitochondrial cristae structure regulation and disease associations.Frontiers in molecular biosciences · 2026Review
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- Systematic profiling reveals distinct senescence signatures and regulators across human brain cell types.Nature communications · 2025Article
- Imbalance in MICOS Proteins in Rat Liver Mitochondria in an Induced Hyperthyroidism Model.Cells · 2025Article
- Therapeutic transplantation of mitochondria and Extracellular Vesicles: Mechanistic insights into mitochondria bioenergetics, redox signaling, and organelle dynamics in preclinical models.Free radical biology & medicine · 2025Review
- Molecular machineries shaping the mitochondrial inner membrane.Nature reviews. Molecular cell biology · 2025Review
131 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The mitochondrial inner membrane (IM) serves as the site for ATP production by hosting the oxidative phosphorylation complex machinery most notably on the crista membranes. Disruption of the crista structure has been implicated in a variety of cardiovascular and neurodegenerative diseases. Here, we characterize ChChd3, a previously identified PKA substrate of unknown function (Schauble, S., King, C. C., Darshi, M., Koller, A., Shah, K., and Taylor, S. S. (2007) J. Biol. Chem. 282, 14952-14959), and show that it is essential for maintaining crista integrity and mitochondrial function. In the mitochondria, ChChd3 is a peripheral protein of the IM facing the intermembrane space. RNAi knockdown of ChChd3 in HeLa cells resulted in fragmented mitochondria, reduced OPA1 protein levels and impaired fusion, and clustering of the mitochondria around the nucleus along with reduced growth rate. Both the oxygen consumption and glycolytic rates were severely restricted. Ultrastructural analysis of these cells revealed aberrant mitochondrial IM structures with fragmented and tubular cristae or loss of cristae, and reduced crista membrane. Additionally, the crista junction opening diameter was reduced to 50% suggesting remodeling of cristae in the absence of ChChd3. Analysis of the ChChd3-binding proteins revealed that ChChd3 interacts with the IM proteins mitofilin and OPA1, which regulate crista morphology, and the outer membrane protein Sam50, which regulates import and assembly of β-barrel proteins on the outer membrane. Knockdown of ChChd3 led to almost complete loss of both mitofilin and Sam50 proteins and alterations in several mitochondrial proteins, suggesting that ChChd3 is a scaffolding protein that stabilizes protein complexes involved in maintaining crista architecture and protein import and is thus essential for maintaining mitochondrial structure and function.
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