New Mechanism for Mitochondrial Elimination via Extracellular Vesicles in Lysosomal Dysfunction
Researchers from the University of California San Diego have made an important discovery in mitochondrial quality control that could reshape our understanding of cardiac homeostasis and disease. Lead author, Dr. Åsa B. Gustafsson, will present these findings at the upcoming congress Targeting EVs in October in Malta.
In their recent study, the team identified a novel pathway for eliminating dysfunctional mitochondria, crucial for maintaining heart function. Traditionally, mitochondria are degraded through lysosomal pathways. However, this research reveals an alternative mechanism that comes into play when lysosomal function is compromised.
The researchers demonstrated that, under conditions of lysosomal inhibition, mitochondria are expelled in large extracellular vesicles (EVs) produced within multivesicular bodies. This process, independent of autophagy, involves the secretion of mitochondria encapsulated in EVs, which are subsequently captured by macrophages. Remarkably, this process does not trigger inflammation, providing a novel insight into cellular waste management.
Further findings highlight that the small GTPase Rab7 plays a critical role in this mechanism. Deletion of Rab7 in cells or adult mouse hearts led to an increased release of EVs containing ubiquitinated cargo, including intact mitochondria. Additionally, elevated levels of these EVs were observed in hearts from aged mice and Danon disease patients, indicating that this vesicular release mechanism becomes more active during cardiac pathophysiology.
This research not only enhances our understanding of mitochondrial quality control but also opens potential avenues for therapeutic interventions in cardiac diseases where lysosomal degradation pathways are impaired.
Join Dr. Åsa B. Gustafsson at Targeting EVs 2024 to know more about how extracellular vesicles could offer new strategies for managing mitochondrial dysfunction in heart disease.
Photo credits: Liang, W., Sagar, S., Ravindran, R. et al. Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired. Nat Commun 14, 5031 (2023).
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