Mitochondrial Fission in Allograft Endothelial Cells: A Novel Actionable Target.

Allograft vascular endothelial cells (ECs) largely remain of donor origin in clinical transplantation (1) and form the primary interface between the recipient and the allograft. Post-transplant, graft ECs sustain normal graft function but also can initiate host anti-graft immune responses(2). Human graft ECs can present both class I and II major histocompatibility molecules, display co-stimulatory ligands that specifically affect memory T cells, and express various adhesion molecules and chemokines responsible for leukocyte recruitment. Many of these EC surface molecules are expressed at low levels or completely absent in resting ECs but may be induced by pro-inflammatory cytokines in the local milieu(2, 3), and EC activation is likely a prerequisite for rejection. However, EC responses to cytokines vary both among and within transplanted organs depending on anatomic location and on exposure to pathological processes, such as ischemia reperfusion injury (IRI). IRI can induce fission and fragmentation of mitochondria, resulting in activation of numerous intracellular and extracellular signaling pathways(4).