Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes, 2021,Crewe et al

Highlights

• Mitochondrial stress stimulates adipocyte sEV release

• Adipocyte stress-induced sEVs are enriched with oxidatively damaged mitochondria

• Mitochondria in sEVs from stressed adipocytes induce a burst of ROS in cardiac tissue

• The adipocyte-derived pro-oxidant signal protects the heart through hormesis

Summary

Adipocytes undergo intense energetic stress in obesity resulting in loss of mitochondrial mass and function. We have found that adipocytes respond to mitochondrial stress by rapidly and robustly releasing small extracellular vesicles (sEVs). These sEVs contain respiration-competent, but oxidatively damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes, where they trigger a burst of ROS. The result is compensatory antioxidant signaling in the heart that protects cardiomyocytes from acute oxidative stress, consistent with a preconditioning paradigm. As such, a single injection of sEVs from energetically stressed adipocytes limits cardiac ischemia/reperfusion injury in mice. This study provides the first description of functional mitochondrial transfer between tissues and the first vertebrate example of “inter-organ mitohormesis.” Thus, these seemingly toxic adipocyte sEVs may provide a physiological avenue of potent cardio-protection against the inevitable lipotoxic or ischemic stresses elicited by obesity.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S155041312100365X

 

Some people wonder why researchers haven't figured out the root cause of ME. Well, the body is immensely complex, with all sorts of subtle but important interactions. We read about these new discoveries, but how much is yet to be discovered?