Non-Canonical Autophagy

Non-Canonical Autophagy

Mechanisms and Pathophysiological Implications
2021, Pages 9-39
Non-Canonical Autophagy

Chapter 2 - AMPK: the energy sensor that regulates autophagy and a potential therapeutic target for neurodegenerative diseases

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Abstract

AMP-activated protein kinase (AMPK) signaling provides a key cellular regulatory system that maintains the balance between energy consumption and production. The heterotrimeric AMPK complex comprising catalytic (α) and regulatory (β and γ) subunits responds to reduced glucose levels by inducing the evolutionarily conserved catabolic process, autophagy, which recycles cytoplasmic content. The protective roles of autophagy induction against a variety of diseases, such as neurodegeneration, has made AMPK activation a promising strategy for therapeutic treatment of various diseases. In this chapter, we describe how AMPK can be induced and how this activates different components of the autophagic machinery. We then review various classes of AMPK activators and the evidence for their capacity to induce autophagy and ameliorate aggregate-prone protein accumulation in cellular and animal models of neurodegeneration.

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  • Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner

    2021, Developmental Cell
    Citation Excerpt :

    Expansion and closure of this structure results in a vesicle known as the autophagosome. Autophagosome biogenesis is induced as a response to various stimuli, including nutrient starvation, leading to the inhibition of the negative autophagy regulator mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and the activation of AMP-activated protein kinase (AMPK) (Karabiyik et al., 2021). This results in the activation of two distinct kinase complexes that initiate phagophore biogenesis—the ULK1 complex and the phosphatidylinositol 3-kinase (PI3K) complex.

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