The Small GTPase Rab7 Regulates Release of Mitochondria in Extracellular Vesicles in Response to Lysosomal Dysfunction
Liang, W.; Diao, R.; Quiles, J.; Najor, R.; Chi, L.; Woodall, B.; Leon, L.; Duran, J.; Cauvi, D.; De Maio, A.; Adler, E.; Gustafsson, A. B.
Show abstract
Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Cardiomyocyte Contractile Impairment in Heart Failure Results from Reduced BAG3-mediated Sarcomeric Protein Turnover 95%
- Mitochondrial CaMKII causes metabolic reprogramming, energetic insufficiency, and dilated cardiomyopathy 95%
- Reproducing extracellular matrix adverse remodelling of non-ST myocardialinfarction in a large animal model 94%
Similar papers in this journal
- LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome 95%
- Pervasive nuclear envelope ruptures precede ECM signaling and disease onset without activating cGAS-STING in Lamin-cardiomyopathy mice 94%
- Chromatin state transition underlies the temporal changes in gene expression during cardiomyocyte maturation 93%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.