ArticleHuman molecular genetics2019
PD-linked CHCHD2 mutations impair CHCHD10 and MICOS complex leading to mitochondria dysfunction.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs.Autophagy · 2026Article
- Microglial CARD19 ameliorates post-stroke neuroinflammation by stabilizing mitochondrial cristae.Neural regeneration research · 2026Article
- Human pluripotent stem cell engineering with CRISPR-Cas9 for Parkinson's disease.Experimental & molecular medicine · 2026Review
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Mitochondrial cristae remodeling: Mechanisms, functions, and pathology.Cell insight · 2025Review
- CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology.Science advances · 2025Article
- A dose-finding study shows terazosin enhanced energy metabolism in neurologically healthy adults.Journal of Parkinson's disease · 2025Article
- Molecular machineries shaping the mitochondrial inner membrane.Nature reviews. Molecular cell biology · 2025Review
- 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
- Dysregulation of mitochondrial α-ketoglutarate dehydrogenase leads to elevated lipid peroxidation in CHCHD2-linked Parkinson's disease models.Nature communications · 2025Article
- Role of the mitochondrial regulatory factor CHCHD2 in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- The MICOS Complex Subunit Mic60 is Hijacked by Intracellular Bacteria to Manipulate Mitochondrial Dynamics and Promote Bacterial Pathogenicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC astrocytes.Acta neuropathologica · 2024Article
- Intracellular delivery of Parkin-RING0-based fragments corrects Parkin-induced mitochondrial dysfunction through interaction with SLP-2.Journal of translational medicine · 2024Article
- CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly inNeural regeneration research · 2024Article
- Involvement of Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2023Review
- SS-31 Improves Cognitive Function in Sepsis-Associated Encephalopathy by Inhibiting the Drp1-NLRP3 Inflammasome Activation.Neuromolecular medicine · 2023Article
- Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: novel opportunities for nanoparticle-based drug delivery.Frontiers in cellular neuroscience · 2023Review
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coiled-coil-helix-coiled-coil-helix domain containing protein 2 (CHCHD2) mutations were linked with autosomal dominant Parkinson's disease (PD) and recently, Alzheimer's disease/frontotemporal dementia. In the current study, we generated isogenic human embryonic stem cell (hESC) lines harboring PD-associated CHCHD2 mutation R145Q or Q126X via clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) method, aiming to unravel pathophysiologic mechanism and seek potential intervention strategy against CHCHD2 mutant-caused defects. By engaging super-resolution microscopy, we identified a physical proximity and similar distribution pattern of CHCHD2 along mitochondria with mitochondrial contact site and cristae organizing system (MICOS), a large protein complex maintaining mitochondria cristae. Isogenic hESCs and differentiated neural progenitor cells (NPCs) harboring CHCHD2 R145Q or Q126X mutation showed impaired mitochondria function, reduced CHCHD2 and MICOS components and exhibited nearly hollow mitochondria with reduced cristae. Furthermore, PD-linked CHCHD2 mutations lost their interaction with coiled-coil-helix-coiled-coil-helix domain containing protein 10 (CHCHD10), while transient knockdown of either CHCHD2 or CHCHD10 reduced MICOS and mitochondria cristae. Importantly, a specific mitochondria-targeted peptide, Elamipretide/MTP-131, now tested in phase 3 clinical trials for mitochondrial diseases, was found to enhance CHCHD2 with MICOS and mitochondria oxidative phosphorylation enzymes in isogenic NPCs harboring heterozygous R145Q, suggesting that Elamipretide is able to attenuate CHCHD2 R145Q-induced mitochondria dysfunction. Taken together, our results suggested CHCHD2-CHCHD10 complex may be a novel therapeutic target for PD and related neurodegenerative disorders, and Elamipretide may benefit CHCHD2 mutation-linked PD.
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