The role of mitochondrial dynamics and cristae remodelling in mitochondrial metabolism and Activation-Induced Cell Death (AICD)

Diplôme Thèse The role of mitochondrial dynamics and cristae remodelling in mitochondrial metabolism and Activation-Induced Cell Death (AICD) eng 2015-05-29 author Corrado Mauro 741452 director Martinou Jean-Claude 27293 director Scorrano Luca 659421 10.13097/archive-ouverte/unige:74322 urn:nbn:ch:unige-743221 Sc. 4790 T lymphocytes amplify and effect the adaptive immune response. To avoid hyper-activation of the immune response, their life and death are tightly regulated. In particular, a second stimulation of the T cell receptor (TCR) leads to the so called Activation-Induced Cell Death (AICD), essential to shut-down the immune response. Evidence is accumulating on the role of mitochondrial morphology and of autophagy in T cell function, but whether these processes participate in AICD is unclear. Here we show that AICD depends on mitochondrial fragmentation and inhibition of autophagy. Mitochondrial fragmentation and cristae remodeling are hallmarks of AICD and their genetic inhibition reduces cytochrome c release and death. Interestingly, during AICD fragmentation crosstalks with autophagy, which is inhibited through a negative AMPK regulation, leading to accumulation of fragmented, dysfunctional mitochondria. Moreover, pharmacological induction of autophagy counteracts the pro-apoptotic features of AICD and protects the cells from death. Thus, efficient AICD depends on the accumulation of fragmented and dysfunctional mitochondria that are excluded from autophagy after restimulation of TCR. Dewey 612 Dewey 570 46 Département de biologie cellulaire 165 134 Département de physiologie cellulaire et métabolisme 21C false 063e107d-2859-4e3c-835c-bbd178eddc41 Thesis Private mauro.pdf 25448462 application/pdf d003d6d1eebda51af47fe99c5286e427ca33ebff076370f388ffee97e16f7350 closedAccess Faculté des sciences / Section de biologie / Département de biologie cellulaire Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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The role of mitochondrial dynamics and cristae remodelling in mitochondrial metabolism and Activation-Induced Cell Death (AICD)				2015	921	0

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Corrado, Mauro