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One of the hallmarks is mitochondrial dysfunction, which is brought about through several pathways: mutations in mitochondrial DNA, elevated reactive oxygen species production, disrupted mitochondrial dynamics and impaired mitophagy. Here, we explore the role of high mobility group box 1 (HMGB1) as a potential contributor to mitochondrial dysfunction, examining how it may influence these pathways through its dual roles as both a protector of mitochondrial integrity and a promoter of inflammatory damage. 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