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

Clair Crewe, Jan Bernd Funcke, Shujuan Li, Nolwenn Joffin, Christy M. Gliniak, Alexandra L. Ghaben, Yu A. An, Hesham A. Sadek, Ruth Gordillo, Yucel Akgul, Shiuhwei Chen, Dmitri Samovski, Pamela Fischer-Posovszky, Christine M. Kusminski, Samuel Klein, Philipp E. Scherer

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1853-1868.e11
JournalCell metabolism
Volume33
Issue number9
DOIs
StatePublished - Sep 7 2021

Keywords

  • adipocyte
  • cardiovascular disease
  • diabetes
  • exosomes
  • extracellular vesicles
  • mitochondria
  • mitochondrial dysfunction
  • mitohormesis
  • obesity
  • stress response

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