Mitochondrial dysfunction in metabolic dysfunction-associated steatotic liver disease: Mechanistic insights and therapeutic horizons (Review)

Metabolic dysfunction‑associated steatotic liver disease (MASLD) has emerged as a central driver of the global chronic liver disease burden. Its progression toward metabolic dysfunction‑associated steatohepatitis and advanced liver fibrosis is shifting from the traditional view of simple lipid accumulation to a dynamic pathogenic network centered on mitochondrial dysfunction. The present review systematically delineates the non‑linear kinetic evolution of mitochondrial alteration from early 'hormetic compensatory adaptation' to late 'bioenergetic collapse' during MASLD progression. The molecular basis of mitochondrial quality control, including fission/fusion dynamics, mitophagy, the mitochondrial unfolded protein response and inter‑organelle cross‑talk via mitochondria‑associated endoplasmic reticulum membranes are critically discussed. Focus is placed on the key homeostatic networks regulated by the sirtuin family (SIRT1‑SIRT7), dissecting their context‑dependent roles and current academic controversies. Finally, contemporary clinical and preclinical therapeutic strategies targeting mitochondrial metabolism are evaluated, providing a strict evidence‑graded translational perspective from basic research toward clinical precision medicine.