Down-regulated TMP21 in Alzheimer's disease induces autophagy via ATG4B activation

摘要

Identification of novel pexophagy regulator Primary cilia mediate mitochondrial stress responses and autophagy to promote cell survival in a Parkinson’s disease model A primary cilium is an antenna-like structure on the cell surface that plays a crucial role in sensory perception and sig- nal transduction. Mitochondria, the ‘powerhouse’ of the cell, are removed by mitochondrial autophagy if they become dys- functional. We show here that mitochondrial stress, caused by respiratory complex inhibitors and excessive fission, robustly stim- ulates ciliogenesis in neuronal, retinal pigment epithelial, and mouse embryonic fibroblast cells. Reactive oxygen species gen- eration, subsequent AMPK activation and autophagy mediate the mitochondrial stress-induced ciliogenesis. Conversely, abro- gation of ciliogenesis compromises mitochondrial stress-induced autophagy leading to enhanced cell death. In mice, treatment with mitochondrial toxin (MPTP) elicits ciliary elongation and autophagy in the substantia nigra dopamine neurons. Blockade of cilia formation in these neurons inhibits MPTP-induced autophagy but facilitates dopamine neuronal loss and motor disability. Our findings demonstrate the important role of primary cilia in cellular pro-survival responses upon mitochondrial stress.