Mitochondrial quality in aging and neurodegeneration: The emerging role of mitochondria-derived vesicles

Mar 7, 2026Mechanisms of ageing and development

Mitochondrial health in aging and brain diseases: The new role of mitochondria-released vesicles

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Abstract

Mitochondria-derived vesicles (MDVs) play a critical role in maintaining mitochondrial integrity and cellular homeostasis.

MDVs are small vesicles that transport damaged mitochondrial components to other cellular compartments.
These vesicles may help delay irreversible mitochondrial damage by enabling rapid responses to stress.
Aging and related disorders are linked to impaired MDV formation and function.
Defective degradation of mitochondrial components can lead to their presence in extracellular vesicles, affecting intercellular signaling.
Alterations in MDV dynamics may be particularly detrimental in the nervous system, where mitochondrial health is crucial.

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Mitochondria are central to cellular energy metabolism, redox balance, and signaling, and their integrity is maintained by a multilayered mitochondrial quality control (MQC) system. This system includes proteostasis, dynamics, biogenesis, and mitophagy, which together repair or remove damaged organelles. Mitochondria-derived vesicles (MDVs) have emerged as an additional MQC component. MDVs are small vesicles that bud from mitochondria and selectively transport damaged mitochondrial proteins, lipids, and nucleic acids to endolysosomal compartments or other intracellular destinations, enabling rapid and localized responses to mitochondrial stress. Acting upstream of or in parallel with mitophagy, MDVs can avoid or delay irreversible mitochondrial damage and help preserve cellular homeostasis. Aging and age-associated disorders are characterized by progressive mitochondrial dysfunction and chronic inflammation. Age-related changes in intracellular trafficking, lysosomal function, and vesicle dynamics may impair MDV formation, cargo selection, and targeting. Under conditions of defective degradation, mitochondrial components may also appear in extracellular vesicles, potentially contributing to altered intercellular signaling and inflammation. In the nervous system, where energetic demands are high and mitochondrial turnover requires tight regulation, such alterations may be especially harmful. This review summarizes MQC mechanisms in neurons, with a focus on MDVs, their dysregulation during aging and neurodegeneration, and implications for biomarkers and therapeutic strategies.

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Mitochondrial quality in aging and neurodegeneration: The emerging role of mitochondria-derived vesicles

Abstract

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