biostudies-literatureCrewe CDeutsche ForschungsgemeinschaftNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNIA NIH HHSNational Institutes of HealthNational Institute on AgingNIH HHS1853-1868.e11https://www.ebi.ac.uk/biostudies/studies/S-EPMC8429176biostudies-literatureUnknown33(9)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 beCell metabolismExtracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes.PMC8429176414232833R01-DK55758P01-AG051459R01-DK127274R00 DK122019R01-DK099110K99DK122019P30 DK020579R01 DK055758Fi1700/7-1R01 DK127274P30 DK056341S10 OD021684S10 OD021685P01 AG051459K01-DK125447RC2 DK118620R01 DK099110K99 DK122019K01 DK125447Akgul YScherer PEGordillo RKlein SFischer-Posovszky PGhaben ALKusminski CMLi SFuncke JBCrewe CGliniak CMSamovski DChen SAn YASadek HAJoffin NfalseExtracellular 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 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 be2021-01-01T00:00:00Z2021 Sep2026-05-28T06:48:36.765Z2025-02-19T03:28:48.733ZS-EPMC84291763441835210.1016/j.cmet.2021.08.002