Molecular medicine reportsOct 30, 2026

Mitochondria problems in fatty liver disease linked to metabolism: Causes and possible treatments

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Nov 2, 2026

Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a significant contributor to global chronic liver disease.

MASLD progresses from simple fat accumulation to more complex conditions like steatohepatitis and advanced liver fibrosis.
Mitochondrial dysfunction evolves through distinct stages, starting with compensatory adaptations and potentially leading to bioenergetic collapse.
Key processes involved in mitochondrial health include the balance of mitochondrial division and fusion, the removal of damaged mitochondria, and the response to stress.
The sirtuin family of proteins plays crucial roles in maintaining mitochondrial function, although their specific effects can vary based on context.
Current therapeutic strategies are exploring ways to target mitochondrial metabolism to improve clinical outcomes in MASLD.

Simplified

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.

Mitochondria problems in fatty liver disease linked to metabolism: Causes and possible treatments

Abstract

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the longevity & aging brief