InflammationJul 7, 2026

Cellular Cleanup of Damaged Mitochondria in Fatty Liver Disease Linked to Metabolism: How It Works, Controls, and Treatment Possibilities

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 8, 2026

Abstract

Metabolic dysfunction-associated fatty liver disease (MASLD) is the most prevalent chronic liver disorder globally.

Insulin resistance, obesity, and gut microbiota imbalance are closely linked to the development of MASLD.
Mitochondrial dysfunction is central to the progression of MASLD.
Mitophagy, which selectively removes damaged mitochondria, is crucial for maintaining cellular health.
Impaired mitophagy may drive the progression of MASLD across various liver cell types.
The regulatory network for mitophagy in MASLD involves key signaling pathways and metabolic changes.
Therapeutic strategies targeting mitophagy include clinical agents, natural compounds, and emerging technologies.

Simplified

Metabolic dysfunction-associated fatty liver disease (MASLD) represents the most prevalent chronic liver disorder globally, with pathogenesis closely linked to insulin resistance, obesity, and gut microbiota dysbiosis. Mitochondrial dysfunction is central to MASLD progression, and mitophagy-a selective form of autophagy that clears damaged mitochondria-plays a crucial role in maintaining cellular homeostasis. This review systematically delineates the molecular mechanisms, regulatory networks, and therapeutic implications of mitophagy in MASLD. We first outline the core machinery of mitophagy, encompassing both ubiquitin-dependent and ubiquitin-independent pathways. We then discuss how impaired mitophagy drives the disease progression of MASLD from the perspective of different hepatic cell types. Furthermore, we summarize the multilayered upstream regulatory network governing mitophagy in the context of MASLD, involving key signaling pathways, metabolic reprogramming, inflammatory cues, epigenetic modifications, and intercellular crosstalk. Finally, we examine therapeutic strategies targeting mitophagy-including clinical and preclinical agents, natural compounds, physical interventions, and emerging technologies-and highlight the challenges posed by its dualistic nature. Moving forward, integrating spatiotemporal dynamics with precision targeting will be essential to translate mitophagy modulation from mechanistic insight into viable clinical therapies for MASLD.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Declarations. Ethics Approval and Consent to Participate: As this study is a narrative review of previously published data, ethical approval was not required by the authors’ institutional review board. Competing Interests: The authors declare no competing interests.

PubMed

Cellular Cleanup of Damaged Mitochondria in Fatty Liver Disease Linked to Metabolism: How It Works, Controls, and Treatment Possibilities

Abstract

Full Text

Funding

Competing interests

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