Does mTORC1 inhibit autophagy at dual stages?

Abstract

Extensive studies have attributed the lysosomal localization of the mechanistic target of rapamycin complex 1 (mTORC1) during its activation. However, the exact biological significance of this lysosomal localization of mTORC1 remains ill‐defined. Interestingly, findings have shown that localization of the lysosome itself is altered under conditions influencing mTORC1 activity. In this perspective, we hypothesize that the localization of mTORC1 and lysosome could be interconnected in a way that manifests regulation of autophagy that is already under progression at the time of mTORC1 activation. This provides a new possibility for autophagy regulation whose complete mechanistic insights remain to be determined.

Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease

“…The mTORC1 complex plays a critical role in regulating autophagy by inhibiting its initiation under nutrient-rich conditions (Ramaian Santhaseela and Jayavelu, 2021). Another key regulator is AMP-activated protein kinase (AMPK), which senses the energy status of cells and triggers autophagy during periods of energy depletion (Gelinas et al, 2018).…”