Autophagy and cell growth – the yin and yang of nutrient responses

Abstract

SummaryAs a response to nutrient deprivation and other cell stresses, autophagy is often induced in the context of reduced or arrested cell growth. A plethora of signaling molecules and pathways have been shown to have opposing effects on cell growth and autophagy, and results of recent functional screens on a genomic scale support the idea that these processes might represent mutually exclusive cell fates. Understanding the ways in which autophagy and cell growth relate to one another is becoming increasingly important, as new roles for autophagy in tumorigenesis and other growth-related phenomena are uncovered. This Commentary highlights recent findings that link autophagy and cell growth, and explores the mechanisms underlying these connections and their implications for cell physiology and survival. Autophagy and cell growth can inhibit one another through a variety of direct and indirect mechanisms, and can be independently regulated by common signaling pathways. The central role of the mammalian target of rapamycin (mTOR) pathway in regulating both autophagy and cell growth exemplifies one such mechanism. In addition, mTOR-independent signaling and other more direct connections between autophagy and cell growth will also be discussed.This article is part of a Minifocus on Autophagy. For further reading, please see related articles: 'Ubiquitin-like proteins and autophagy at a glance' by Tomer Shpilka et al. (J. Cell Sci. 125, 2343-2348 and 'Autophagy and cancer -issues we need to digest' by Emma Liu and Kevin Ryan (J. Cell Sci. 125, 2349-2358).

Ambra1 at a glance

“…First, a plethora of signaling molecules and pathways have been shown to have opposite effects on cell growth and autophagy, supporting the idea that these processes might represent mutually exclusive cell fates (Neufeld, 2012). This reciprocal inhibition between autophagy and cell growth can occur either through direct regulative mechanisms, most of which remain to be determined to date, or through the same signaling pathways that act independently and simultaneously on autophagy and cell growth.…”

The peiminine stimulating autophagy in human colorectal carcinoma cells via AMPK pathway by SQSTM1

“…Taken together, these results indicate that peiminine-mediated tumor growth inhibition is associated with apoptosis and autophagic cell death. that when autophagosomes fusion with lysosomes, the formation of autolysosomes ensures the degradation and supplement of recycled energy, as in the case of starvation [20]. Activation of autophagy further contributes to the tolerance of nutrient deprivation in colorectal carcinoma [21,22].…”

Two-pore channel 1 interacts with citron kinase, regulating completion of cytokinesis

“…This process releases the breakdown products as nutrients that can be reused by the cell or exported for use by other cells. 51 Interestingly, mTOR is central in regulating the balance between autophagy and cell growth, 51 and tpc1/tpc2 double knockout mice showed defects in autophagy. 22 Autophagy was also recently shown to play a critical role in the degradation of active RhoA, with implications for cytokinesis control and genomic stability.…”