Novel Pathway Unveiled: Cardiac Cells Release Mitochondria in Extracellular Vesicles to Safeguard Heart Health
Overview of EV secretion in cells (Created with BioRender.com)
Researchers from the University of California San Diego have identified a previously unknown mechanism employed by cardiac cells to maintain mitochondrial quality control when lysosomal function is compromised. Mitochondria, responsible for generating the energy required for cardiac contraction, are crucial for maintaining cardiac homeostasis. Dysfunctional mitochondria are typically eliminated through intracellular degradation pathways that converge on the lysosome.
The study, published in Nature Communications, unveils an alternative pathway activated in response to lysosomal inhibition, leading to the secretion of mitochondria in large extracellular vesicles (EVs). Unlike traditional degradation routes, this novel mechanism involves the release of mitochondria in EVs produced within multivesicular bodies. Importantly, this process is independent of autophagy, revealing a previously unrecognized cellular strategy for mitochondrial disposal.
The research team demonstrated that the deletion of the small GTPase Rab7 in cells or adult mouse hearts resulted in an increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. Notably, the secreted EVs were efficiently captured by macrophages without inducing inflammation, highlighting the potential of this pathway as a safe means of mitochondrial elimination.
Further investigations revealed that hearts from aged mice or individuals with Danon disease exhibited elevated levels of secreted EVs containing mitochondria. This indicates the activation of the vesicular release pathway during cardiac pathophysiology, shedding light on its relevance in conditions associated with compromised lysosomal function.
These findings redefine our understanding of mitochondrial quality control in cardiac cells and establish that, when lysosomal degradation is hindered, mitochondria are eliminated in large extracellular vesicles through the endosomal pathway.
This discovery not only expands our knowledge of cellular mechanisms but also holds potential implications for future therapeutic strategies aimed at preserving cardiac health. The research opens up new avenues for investigating the role of extracellular vesicles in cardiac pathophysiology and may pave the way for innovative treatments targeting mitochondrial dysfunction in heart-related conditions.
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