Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response

• DOI: 10.1016/j.celrep.2021.109076
• Publication Date: 2021-05-04T14:30:24Z
• Authors: Silvia Vaena; Paramita Chakraborty; Han Gyul Lee; Alhaji H. Janneh; Mohamed Faisal Ka...; Gyda Beeson; Zachariah Hedley; Ahmet Yalcinkaya; M. Hanief Sofi; Hong Li; Monica L. Husby; Robert V. Stahelin; Xue-Zhong Yu; Shikhar Mehrotra; Besim Ogretmen
• Keywords: Ceramide synthase; Sphingolipid

We lack a mechanistic understanding of aging-mediated changes in mitochondrial bioenergetics and lipid metabolism that affect T cell function. The bioactive sphingolipid ceramide, induced by aging stress, mediates mitophagy death; however, the aging-related roles ceramide regulating function remain unknown. Here, we show activated cells isolated from mice have elevated C14/C16 accumulation mitochondria, generated synthase 6, leading to mitophagy/mitochondrial dysfunction. Mechanistically, aging-dependent inhibits protein kinase A, cells. This aging/ceramide-dependent attenuates antitumor functions vitro vivo. Also, inhibition or PKA activation genetic pharmacologic means prevents restores central memory phenotype Thus, these studies help explain mechanisms behind dysregulation cells' activity, which can be restored inhibiting ceramide-dependent mitophagy.