ArticleHuman molecular genetics2018
In vitro and in vivo studies of the ALS-FTLD protein CHCHD10 reveal novel mitochondrial topology and protein interactions.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 119 citations in OpenAlex.
- CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs.Autophagy · 2026Article
- Frontotemporal dementia associated CHCHD10Cell death & disease · 2026Article
- The CDKL5 kinase undergoes liquid-liquid phase separation driven by a serine-rich C-terminal region.Life science alliance · 2026Article
- Pregnancy precipitates metabolic imbalance and accelerates death in an animal model of mitochondrial cardiomyopathy.Molecular metabolism · 2026Article
- Mitochondrial cristae remodeling: Mechanisms, functions, and pathology.Cell insight · 2025Review
- Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies.Stem cell research & therapy · 2025Review
- CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology.Science advances · 2025Article
- The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain.Cell death & disease · 2025Article
- Clinical, neuropathological, and biochemical characterization of ALS in a large CHCHD10 R15L family.medRxiv : the preprint server for health sciences · 2025Article
- Molecular machineries shaping the mitochondrial inner membrane.Nature reviews. Molecular cell biology · 2025Review
- Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.Nature communications · 2025Article
- Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- Dose-dependent CHCHD10 dysregulation dictates motor neuron disease severity and alters creatine metabolism.Acta neuropathologica communications · 2025Article
- CHCHD4 Oxidoreductase Activity: A Comprehensive Analysis of the Molecular, Functional, and Structural Properties of Its Redox-Regulated Substrates.Molecules (Basel, Switzerland) · 2025Review
- The Mia40 substrate Mix17 exposes its N-terminus to the cytosolic side of the mitochondrial outer membrane.Journal of cell science · 2025Article
- Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dysregulation of mitochondrial α-ketoglutarate dehydrogenase leads to elevated lipid peroxidation in CHCHD2-linked Parkinson's disease models.Nature communications · 2025Article
- Modulation of Mitochondria-Endoplasmic Reticulum Contacts (MERCs) by Small Molecules as a New Strategy for Restoring Lipid Metabolism in an Amyotrophic Lateral Sclerosis Model.Journal of medicinal chemistry · 2025Article
- The Underestimated Role of Iron in Frontotemporal Dementia: A Narrative Review.International journal of molecular sciences · 2024Review
- Rethinking antisense oligonucleotide therapeutics for amyotrophic lateral sclerosis.Annals of clinical and translational neurology · 2024Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Mutations in coiled-coil-helix-coiled-coil-helix-domain containing 10 (CHCHD10), a mitochondrial twin CX9C protein whose function is still unknown, cause myopathy, motor neuron disease, frontotemporal dementia, and Parkinson's disease. Here, we investigate CHCHD10 topology and its protein interactome, as well as the effects of CHCHD10 depletion or expression of disease-associated mutations in wild-type cells. We find that CHCHD10 associates with membranes in the mitochondrial intermembrane space, where it interacts with a closely related protein, CHCHD2. Furthermore, both CHCHD10 and CHCHD2 interact with p32/GC1QR, a protein with various intra and extra-mitochondrial functions. CHCHD10 and CHCHD2 have short half-lives, suggesting regulatory rather than structural functions. Cell lines with CHCHD10 knockdown do not display bioenergetic defects, but, unexpectedly, accumulate excessive intramitochondrial iron. In mice, CHCHD10 is expressed in many tissues, most abundantly in heart, skeletal muscle, liver, and in specific CNS regions, notably the dopaminergic neurons of the substantia nigra and spinal cord neurons, which is consistent with the pathology associated with CHCHD10 mutations. Homozygote CHCHD10 knockout mice are viable, have no gross phenotypes, no bioenergetic defects or ultrastructural mitochondrial abnormalities in brain, heart or skeletal muscle, indicating that functional redundancy or compensatory mechanisms for CHCHD10 loss occur in vivo. Instead, cells expressing S59L or R15L mutant versions of CHCHD10, but not WT, have impaired mitochondrial energy metabolism. Taken together, the evidence obtained from our in vitro and in vivo studies suggest that CHCHD10 mutants cause disease through a gain of toxic function mechanism, rather than a loss of function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.