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This study investigated whether in\u00a0vitro hyperpolarized (HP) [2\u2010\n                    <jats:sup>13<\/jats:sup>\n                    C]pyruvate NMR spectroscopy can identify a mitochondria\u2010active HCC phenotype and assess its association with sensitivity to mitochondrial metabolic inhibition. HP [2\u2010\n                    <jats:sup>13<\/jats:sup>\n                    C]pyruvate NMR spectroscopy was used to evaluate mitochondrial metabolism in McA\u2010RH7777 HCC cells, with N1S1 cells serving as a glycolysis\u2010dominant reference. Cell viability following treatment with the glutaminase inhibitor BPTES and the mitochondrial metabolic inhibitor CPI\u2010613 was assessed by MTT assay, and metabolic changes following CPI\u2010613 treatment were further evaluated using HP [2\u2010\n                    <jats:sup>13<\/jats:sup>\n                    C]pyruvate. HP [2\u2010\n                    <jats:sup>13<\/jats:sup>\n                    C]pyruvate demonstrated enhanced pyruvate\u2010to\u2010glutamate conversion in McA\u2010RH7777 cells, whereas N1S1 showed minimal glutamate labeling. CPI\u2010613 treatment resulted in a dose\u2010dependent reduction in cell viability, while BPTES produced limited effects. Although pyruvate\u2010to\u2010glutamate conversion did not significantly decrease following CPI\u2010613 treatment, pyruvate\u2010to\u2010lactate conversion increased, indicating metabolic adaptation. These findings demonstrate that HP [2\u2010\n                    <jats:sup>13<\/jats:sup>\n                    C]pyruvate enables functional identification of a mitochondria\u2010active HCC phenotype characterized by enhanced pyruvate\u2010to\u2010glutamate conversion. This approach may facilitate metabolic subtype classification, help identify tumors susceptible to mitochondrial metabolic inhibition, and enable non\u2010invasive monitoring of treatment\u2010induced metabolic adaptation.\n                  <\/jats:p>","DOI":"10.1002\/nbm.70360","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:34:28Z","timestamp":1785929668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperpolarized [2\u2013\n                    <sup>13<\/sup>\n                    C]Pyruvate Identifies a Mitochondria\u2010Active Hepatocellular Carcinoma Phenotype With Vulnerability to Mitochondrial Inhibition"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-4858","authenticated-orcid":false,"given":"Qianhui","family":"Dou","sequence":"first","affiliation":[{"name":"Athinoula A. 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