CD8A and viral infectious disease: During primary response to virus infection, CD8+ T cells downregulate NIX expression as a reaction to the T cell antigen receptor (TCR) signal, leading to insufficient mitophagy and buildup of depolarized mitochondria, which generates superoxide to activate CD8+ T cells.327 However, antigen-specific CD8+ T cells boost the expression of NIX to remove depolarized mitochondria undergoing contraction state, thereby promoting CD8+ T effector memory cells to form.