Mitochondrial acquisition after the Asgard revolution: Reconstructing eukaryogenesis with insights for mitochondrial transplantation

Mitochondria arose from an alphaproteobacterial endosymbiont that became integrated within an archaeal host during eukaryogenesis. The discovery of Asgard archaea has clarified host ancestry and supports reconstructions in which aspects of cytoskeletal and membrane complexity preceded mitochondrial acquisition. Organellogenesis involved genome reduction, gene transfer, protein import, metabolic coupling, and vertical inheritance. These evolutionary principles complement current mitochondrial transplantation recommendations by generating testable predictions about recipient dependence and the duration of rescue. Transplanted mitochondria are mature organelles introduced into cells already equipped to maintain mitochondria; the requirement for transient or durable function must nevertheless be tested for each indication. Aging can modify organelle delivery, recipient quality control, and tissue responses, with particular implications for the neurovascular unit and neuronal function. Extracellular vesicle delivery requires verification of mitochondrial cargo, potency, and compatibility. Measurable criteria distinguish delivery, uptake, cytosolic access, network interaction, persistence, and functional benefit, while separating evidence from aging, acute ischemia, and inherited disease models.