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Mitochondrial dysfunction underlies ALS pathology and represents a potential therapeutic target. Here, we demonstrated the therapeutic potential of mitochonic acid 5 (MA-5), a novel mitochondria-targeted compound that ameliorated ALS phenotypes by enhancing mitochondrial function. In a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    ALS model expressing a mutant human\n                    <jats:italic>SOD1<\/jats:italic>\n                    (G85R), MA-5 significantly improved locomotor activity, with a trend toward restoration of mitochondrial integrity. In skin fibroblasts derived from ALS patients and motor neurons derived from induced pluripotent stem cells, MA-5 restored ATP production and increased mitochondrial motility. Multiomics analyses suggested that MA-5 modulated mitochondria-linked gene expression and downregulated the glycerophosphate shuttle, contributing to mitochondrial reactive oxygen species production. Transcriptomic analysis identified\n                    <jats:italic>C7orf31<\/jats:italic>\n                    as a potential marker for monitoring the therapeutic effects of MA-5 and diagnosing ALS subtypes. These findings support MA-5 as a promising therapeutic candidate for ALS and propose\n                    <jats:italic>C7orf31<\/jats:italic>\n                    as a potential biomarker for treatment monitoring and for disease subtyping.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.200761","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:01:08Z","timestamp":1790013668000},"source":"Crossref","is-referenced-by-count":0,"title":["Mitochonic acid 5 alleviates amyotrophic lateral sclerosis phenotypes via mitochondrial augmentation"],"prefix":"10.1172","volume":"11","author":[{"given":"Yoshitsugu","family":"Oikawa","sequence":"first","affiliation":[{"name":"Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan."},{"name":"Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, 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