More recently, we have refined these observations and demonstrated CD8+ effector-memory T cells (CD8+ TEM) to be particularly vulnerable to LOF heteroplasmy (13), suggesting that activation and expansion of naive CD8+ T cells, in particular, require intact mitochondrial genetic integrity, relative to other immune cells as further corroborated by other groups including in a mouse model of mitochondrial disease (16, 17). Here, CD8A is linked to mitochondrial disease.