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ATPIF1, the rheostat in mitochondrial bioenergetics and dysfunction in diseases

Year: 2026
Type: review
Abstract: ATP synthase inhibitory factor 1 (ATPIF1) is a critical regulator of the activity of F1F0-ATPase, a central enzyme in mitochondrial ATP production. Accumulating evidence highlights ATPIF1 as a master modulator of mitochondrial morphology, function, cellular metabolism, and stress responses in diverse physiological and pathological conditions. In this review, we first provide a brief overview of mitochondrial structure and ATP production. We then focus on the cellular and molecular mechanisms of mitochondrial bioenergetics regulated by ATPIF1 and emphasize the role of ATPIF1 in energy preservation, mitophagy and redox balance. Furthermore, we comprehensively summarize recent advances about the pathological function of ATPIF1 in various mitochondrial dysfunction related diseases, including ischemia/reperfusion injury, aging, cancer, sepsis and chronic inflammation, and neurodegenerative disorders. ATP1IF1, the mitochondrial rheostat, emerges as a novel therapeutic target to combat mitochondrial dysfunction across multiple organ systems.
DOI: 10.1016/j.mito.2026.102187
Institutions: Augusta University, Wuhan University, Renmin Hospital of Wuhan University, Shanghai Changzheng Hospital, Zhengzhou University, First Affiliated Hospital of Zhengzhou University, Shanghai Jiao Tong University, Shanghai Sixth People's Hospital
Language: English
Open Access status: hybrid
Estimated APC paid: $3,220
OpenAlex ID: W7166351912
FWCI:
Cites: 86
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Related to: 10