{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHCHD10 is a mitochondrial intermembrane space protein that is critically enriched at cristae junctions and is a core component of the mitochondrial contact site and cristae organizing system (MICOS) complex. Multiple studies demonstrate that CHCHD10 helps maintain mitochondrial architecture by preserving proper cristae structure, ensuring mitochondrial genome stability, and supporting the assembly and function of respiratory chain complexes (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In neuronal and muscle cells, CHCHD10 is essential for optimal mitochondrial energy metabolism and, by extension, for the maintenance of synaptic and neuromuscular integrity. Perturbations in its function—whether by loss of function or by toxic gain‐of‐function mutations—lead to mitochondrial fragmentation, disorganization of cristae, impaired oxidative phosphorylation (notably via deficiencies in Complex I assembly), and mitochondrial DNA instability. Such defects have been implicated in a spectrum of neuromuscular and neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), mitochondrial myopathy, and even aspects of Parkinson’s disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": " Furthermore, CHCHD10 forms heteromeric complexes with its paralog CHCHD2, and alterations in the stability or assembly of these complexes directly compromise mitochondrial respiration and trigger stress responses that further impact cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": " Variability in clinical phenotypes—from motor neuron disease and variable neuromuscular presentations to cognitive and frontotemporal symptoms—appears to stem from the degree of CHCHD10 dysfunction, underscoring its central role in ensuring mitochondrial integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sylvie Bannwarth, Samira Ait-El-Mkadem, Annabelle Chaussenot, et al. 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