Revitalizing mitochondrial quality control: targeting mitochondria-derived vesicles in Parkinson’s disease

Mar 31, 2026Biochemical pharmacology

Improving cell power supply cleanup by targeting small mitochondrial vesicles in Parkinson's disease

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Abstract

Impaired mitochondrial quality control is implicated as a central driver of Parkinson's disease pathogenesis.

Parkinson's disease is characterized by the loss of dopaminergic neurons in the midbrain.
Mitochondrial quality control maintains mitochondrial integrity through processes like biogenesis and degradation.
Mitochondria-derived vesicles (MDVs) transport damaged mitochondrial components for degradation, providing a rapid quality control mechanism.
MDVs also play roles in signaling between organelles and communication between cells, impacting neuronal stability.
Disruption of MDV biogenesis and clearance is linked to mitochondrial dysfunction and neurodegeneration in Parkinson's disease.

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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the midbrain substantia nigra, resulting in debilitating motor and non-motor symptoms. No disease modifying therapy is currently available for PD patients. Mounting evidence implicates impaired mitochondrial quality control (MQC) as a central driver of PD pathogenesis. MQC maintains mitochondrial integrity and function through coordinated mechanisms such as mitochondrial biogenesis, dynamics, mitophagy, the ubiquitin-proteasome system, and the formation of mitochondria-derived vesicles (MDVs). MDVs are small vesicular structures that selectively sequester and transport damaged mitochondrial components to lysosomes for degradation, representing a rapid and localized quality control pathway distinct from mitophagy. Beyond their degradative role, MDVs also participate in inter-organelle signalling and intercellular communication, suggesting a broader influence on neuronal homeostasis. Disruption of MDV biogenesis, trafficking, or clearance has been emerging as a key contributor of mitochondrial dysfunction and neurodegeneration in PD. This review synthesizes current understanding of MDV biology, its integration within the MQC network, role in PD pathogenesis and explores how targeting MDV pathways may offer novel diagnostic and therapeutic strategies to modify disease progression in PD.

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Revitalizing mitochondrial quality control: targeting mitochondria-derived vesicles in Parkinson’s disease

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