The study by Spees et al. investigates the potential for mitochondrial transfer between cells to rescue aerobic respiration in mammalian cells with nonfunctional mitochondria. Mitochondria, essential organelles responsible for oxidative phosphorylation and other vital processes, can be transferred between adult stem cells and somatic cells. The researchers used A549 ρ− cells, which lack functional mitochondria and cannot undergo aerobic respiration, to demonstrate that these cells can be rescued by co-culture with human bone marrow (hMSCs) or skin fibroblasts. The rescued cells exhibited exponential growth, normal mitochondrial protein expression, and restored mitochondrial function, as evidenced by increased ATP levels, reduced lactate production, decreased reactive oxygen species, and higher membrane potential and oxygen consumption. Genetic analysis confirmed the transfer of functional mitochondria without evidence of cell fusion. The findings suggest that active mitochondrial transfer could explain the beneficial effects observed in animal models of diseases such as spinal cord injury, stroke, and heart disease, where large numbers of hMSCs or other progenitor cells are administered.The study by Spees et al. investigates the potential for mitochondrial transfer between cells to rescue aerobic respiration in mammalian cells with nonfunctional mitochondria. Mitochondria, essential organelles responsible for oxidative phosphorylation and other vital processes, can be transferred between adult stem cells and somatic cells. The researchers used A549 ρ− cells, which lack functional mitochondria and cannot undergo aerobic respiration, to demonstrate that these cells can be rescued by co-culture with human bone marrow (hMSCs) or skin fibroblasts. The rescued cells exhibited exponential growth, normal mitochondrial protein expression, and restored mitochondrial function, as evidenced by increased ATP levels, reduced lactate production, decreased reactive oxygen species, and higher membrane potential and oxygen consumption. Genetic analysis confirmed the transfer of functional mitochondria without evidence of cell fusion. The findings suggest that active mitochondrial transfer could explain the beneficial effects observed in animal models of diseases such as spinal cord injury, stroke, and heart disease, where large numbers of hMSCs or other progenitor cells are administered.