• Mitochondrial dysfunction impairs adipocyte browning by suppressing UCP1 expression and disrupting key signaling pathways (PPAR-γ/PGC-1α and AMPK/mTOR), leading to reduced energy expenditure and insulin resistance.
• The review highlights the intersection of mitochondrial dysfunction with neurodegenerative disorders via oxidative stress, suggesting a systemic link between metabolic and neurological diseases.
• Structural mitochondrial anomalies and mtDNA-nuclear DNA crosstalk complicate therapeutic targeting, emphasizing the need for advanced research approaches.
• Future precision therapies, such as gene editing and single-cell omics, hold promise for restoring mitochondrial function and enhancing adipocyte browning to combat obesity and related metabolic syndromes.