Nicholas Ktistakis
Research Summary
Autophagy (from the Greek self-eating) is a cellular mechanism which generates nutrients for the cell, primarily during times of starvation. Autophagy is also used to eliminate cell material that becomes damaged, leading to a periodic clean-up of the cell interior. Although it is a response by single cells, it is also very important for the health of an organism.
When autophagy is suppressed cells exhibit signs of oxidative damage because their dysfunctional mitochondria cannot be removed and continue to produce reactive oxygen species. Similarly, suppression of autophagy causes the build-up of mutant proteins that cause neurodegenerative disorders.
Autophagy is also critical for the neonatal period: animals which lack autophagy die soon after birth because they cannot generate nutrients during that time. Finally, autophagy is critical for the extension of lifespan in all organisms studied, and is therefore a significant factor that affects healthy ageing. The pathway of autophagy starts when a novel double membrane vesicle called an autophagosome is formed in the cell interior.
We have shown that one of the signals for formation of autophagosomes is the synthesis of a lipid called PI3P which leads to formation of omegasomes. These are membrane extensions of the endoplasmic reticulum, from which some autophagosomes emerge. We are studying exactly how this happens, both in terms of signals and of how the intermediate structures eventually lead to an autophagosome.
I was very happy to speak at the University of Michigan Protein Folding Diseases seminar series recently. This talk provides a nice summary of the current work in my lab:
Latest Publications
Sorting nexin 5 mediates virus-induced autophagy and immunity. Nature, 1, 1, 16 Dec 2020 PMID: 33328639 |
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CDK1, the Other 'Master Regulator' of Autophagy. Trends in cell biology, 1, 1, 30 Nov 2020 PMID: 33272830 |
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Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform. Developmental cell, 55, 2, 26 Oct 2020 PMID: 33108756 |