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

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Scorano, Luca
Defense Thèse de doctorat : Univ. Genève, 2015 - Sc. 4790 - 2015/05/29
Abstract 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.
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URN: urn:nbn:ch:unige-743221
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CORRADO, Mauro. The role of mitochondrial dynamics and cristae remodelling in mitochondrial metabolism and Activation-Induced Cell Death (AICD). Université de Genève. Thèse, 2015. https://archive-ouverte.unige.ch/unige:74322

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Deposited on : 2015-07-27

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