Molecular neurobiologyJul 9, 2026

Small Protein Tagging in Mitochondrial Quality Control and Its Role in Brain Degeneration Diseases

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 10, 2026

Abstract

The small ubiquitin-like modifier (SUMO) pathway is identified as a key regulator of mitochondrial quality control in neurons.

Mitochondria are essential for energy generation in neurons and are susceptible to damage due to their long lifespan.
A mitochondrial quality control system maintains healthy mitochondria by managing processes like biogenesis, fission, fusion, and the removal of damaged components.
Dysregulation of the SUMO pathway can lead to mitochondrial dysfunction, which is associated with neurodegenerative diseases.
The review focuses on the SUMO pathway's role in mitochondrial quality control and its implications for Alzheimer's, Parkinson's, and Huntington's diseases.
Therapeutic strategies targeting the SUMO pathway may offer potential solutions for treating neurodegenerative diseases, though challenges remain.

Simplified

Mitochondria, as the primary energy-generating organelles in neurons, play a pivotal role in regulating cellular metabolism. Given the post-mitotic nature and long lifespan of neurons, they are particularly vulnerable to the cumulative burden of mitochondrial damage. In response to various physiological and stress signals, a sophisticated mitochondrial quality control (MQC) system has evolved, which encompasses mitochondrial biogenesis, dynamics (fission and fusion), and mitophagy. This coordinated network acts as a critical surveillance mechanism to eliminate damaged components and maintain a healthy mitochondrial pool. The small ubiquitin-like modifier (SUMO) pathway, involving reversible SUMOylation and deSUMOylation, has emerged as a key regulator of MQC by directly modifying its core components. Dysregulation of the SUMO pathway disrupts mitochondrial homeostasis, and the resulting mitochondrial dysfunction is increasingly recognized as a central pathogenic mechanism in neurodegenerative diseases. This review systematically examines the role of the SUMO pathway in regulating MQC and its implications in the pathogenesis of Alzheimer's disease, Parkinson's disease, and Huntington's disease. Finally, we discuss the therapeutic potential and translational challenges of targeting the SUMO pathway for the treatment of neurodegenerative diseases.

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Competing interests

Declarations. Competing interests: The authors declare no competing interests.

PubMed

Small Protein Tagging in Mitochondrial Quality Control and Its Role in Brain Degeneration Diseases

Abstract

Full Text

Funding

Competing interests

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