Figure 2.

Distinct factors regulate autophagy among different cell types of the nervous system. In each of the cells which comprise the central and peripheral nervous systems, autophagy is differentially regulated by cell type-specific effectors. In neurons (top left), modulation of SPHK1 by phenoxazine compounds such as 10-NCP, but not starvation, potently induces autophagy. In contrast, nutrient deprivation is sufficient to promote SPHK1 signaling and autophagy induction in astrocytes (top center). In the axonal compartment of neurons, KIF1A and PINK1-PRKN are critical for facilitating local autophagic activity (left, middle). MicroRNAs such as MIR101 and MIR195 suppress oligodendrocytic and Schwann cell autophagy, respectively (right). Schwann cells also clear myelin debris through myelinophagy, a unique form of selective autophagy that is dependent on FIG4 (bottom). In muscle, specific transcription factors can exert activating (FOXO3) or suppressive (PPARGC1A, RUNX1) effects on autophagy, and phosphatases such as MTM1 and MTMR14 inhibit autophagy by recycling phosphoinositides needed for autophagy induction (bottom left).