This review synthesizes current knowledge of mitochondria-derived vesicles (MDVs) as a distinct mitochondrial quality control pathway—covering MDV biogenesis, trafficking, clearance, roles in inter-organelle signaling and intercellular communication—and links MDV dysfunction to Parkinson's disease…

By highlighting MDVs as an actionable, mitophagy-independent mechanism for selective mitochondrial repair and clearance, the paper identifies novel targets and biomarker opportunities that could enable mitochondria-focused, disease-modifying interventions for PD.

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.