Arming a killer: mitochondrial regulation of CD8+T cell cytotoxicity

While once regarded as ATP factories, mitochondria have taken the spotlight as important regulators of cellular homeostasis. The past two decades have witnessed an intensifying interest in the study of mitochondria in cells of the immune system, with many new and unexpected roles for mitochondria emerging. Immune cells offer intriguing insights as mitochondria appear to play different roles at different stages of T cell development, matching the changing functions of the cells. Here we briefly review the multifaceted roles of mitochondria during T cell differentiation, focusing on CD8+ cytotoxic T lymphocytes (CTLs) and we consider how mitochondrial dysfunction can contribute to CTL exhaustion. In addition, we highlight a newly appreciated role for mitochondria as homeostatic regulators of CTL-mediated killing and explore the emerging literature describing mechanisms linking cytosolic and mitochondrial protein synthesis.

Automated summary

Mitochondria, once viewed as ATP factories, have now been recognized as crucial regulators of cellular homeostasis. Recent research has revealed multiple roles of mitochondria in immune system cells, particularly in T cell differentiation and function. This article provides an overview of the diverse functions of mitochondria during T cell development, with a focus on CD8+ cytotoxic T lymphocytes (CTLs), and explores the impact of mitochondrial dysfunction on CTL exhaustion. Additionally, it highlights the newfound role of mitochondria as homeostatic regulators of CTL-mediated killing and discusses the mechanisms linking cytosolic and mitochondrial protein synthesis.