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Kundu: Characterization of signals involved in targeting mitochondria for autophagic degradation

My lab uses reticulocyte maturation as a model system and we are currently focusing on elucidating the role of autophagy in degrading mitochondria. Autophagy is a catabolic process in which cellular components are sequestered in double-membrane autophagosomes and delivered to the lysosome for degradation and recycling of essential components.  Although autophagy has been considered a non-specific process, there is growing evidence that organelles, including mitochondria, can be specifically targeted by components of the general autophagy machinery. The proteins involved in regulating autophagy have been elucidated in yeast over the past decade, while the roles of their mammalian counterparts are only beginning to be understood. Atg1 is a serine/threonine kinase whose involvement in the induction of autophagy, and more specifically in the switch between selective and non-selective autophagy, has been well characterized in yeast. Two mammalian homologues of Atg1 have been identified, but their roles in autophagy have not been well characterized.  We are currently in the process of dissecting the role of Ulk1 and Ulk2 in autophagy in vitro and in vivo. Towards this end, we have generated mice harboring conditional knock-outs of both Ulk1 and Ulk2. Examination of the subcellular localization and interacting partners of Ulk1 and Ulk2 under various stimuli will provide additional insight into the normal function of the Atg1 homologues.