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Here, we have evaluated the activity of hydroxyhydroquinone (HHQ) as a novel modulator of mitochondrial metabolism. Molecular simulations revealed that HHQ can act as an alternative aromatic substrate for human COQ2 in the CoQ\n                    <jats:sub>10<\/jats:sub>\n                    biosynthetic pathway. In cultured cells, HHQ exposure (5.10\n                    <jats:sup>\u2212\u20095<\/jats:sup>\n                    mol.L\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    ) enhanced complex I activity while maintaining stable ATP levels. HHQ reduced nitric oxide accumulation without altering superoxide dismutase activity, suggesting selective redox modulation. By bypassing the 4-hydroxybenzoic acid (PHBA) pathway, HHQ restores mitochondrial homeostasis and supports aerobic metabolism. These findings highlight HHQ as a small aromatic compound with strong redox potential that may favor metabolic functions driven by CoQ\n                    <jats:sub>10<\/jats:sub>\n                    deficiency and mitochondrial dysfunction.\n                  <\/jats:p>","DOI":"10.1007\/s11010-026-05687-8","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T09:18:15Z","timestamp":1786094295000},"page":"4611-4628","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydroxyhydroquinone as a novel modulator of mitochondrial metabolism with potential to restore CoQ10 homeostasis"],"prefix":"10.1007","volume":"481","author":[{"given":"Paulo Roberto","family":"dos Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Rastegar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3339-1901","authenticated-orcid":false,"given":"Mariana","family":"Roesch-Ely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"5687_CR1","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1080\/09168451.2017.1301802","volume":"81","author":"S Soga","year":"2017","unstructured":"Soga S, Ota N, Shimotoyodome A (2017) Reduction in hydroxyhydroquinone from coffee increases postprandial fat utilization in healthy humans: a randomized double-blind, cross-over trial. 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