Intercellular mitochondria transfer rescues aerobic respiration in metabolically compromised macrophages in vitro and in vivo

Abstract Mitochondria evolved through an ancient endosymbiotic process and are essential for eukaryotic cellular metabolism. An emerging body of literature indicates that some cells export mitochondria delivery to other cells, a termed intercellular transfer. Recently, we demonstrated adipocytes transfer macrophages in vivo this maintains white brown adipose tissue homeostasis (Brestoff et al., Cell Metab, 2021; Rosina 2022; Borcherding/Jia 2022). It is believed degrade exogenous as form licensed mitophagy supports adipocyte quality control, however it unclear whether externally-derived able respire once captured. We administered purified wildtype (WT) or NDUFS4 KO mice, which lack enzyme required mitochondrial Complex I activity. Although WT peritoneal quickly degraded mitochondria, captured, retained, utilized rescue cell-intrinsic defects aerobic respiration. Similarly, healthy BV2 microglial captured vitro, but exposed rotenone Antimycin A the toxin-induced Purified from mice failed respiration toxin-stressed cells. These data suggest with defective metabolism can obtain utilize exogenous, cell-free their environment overcome metabolic crisis. Supported by grant Burroughs Wellcome Fund (CAMS #1019648) JRB.