Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes

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 extra cellular 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.

Automated summary

Adipocytes under energetic stress release sEVs containing damaged mitochondrial particles, which enter circulation and trigger antioxidant signaling in cardiomyocytes, protecting them from oxidative stress. This functional mitochondrial transfer between tissues provides potent cardio-protection against stresses induced by obesity.