Surviving Starvation: AMPK Protects Germ Cell Integrity by Targeting Multiple Epigenetic Effectors

Abstract

Acute starvation can have long-term consequences that are mediated through epigenetic change. Some of these changes are affected by the activity of AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. In Caenorhabditis elegans, the absence of AMPK during a period of starvation in an early larval stage results in developmental defects following their recovery on food, while many of them become sterile. Moreover, the loss of AMPK during this quiescent period results in transgenerational phenotypes that can become progressively worse with each successive generation. Our recent data describe a chromatin-based mechanism of how AMPK mediates adjustment to acute starvation in the germ cells, however, the heritable aspect of this AMPK mutant phenotype remains unresolved. Here, we explore how AMPK might affect this process and speculate how the initial transcription that occurs in the germ cells may adversely affect subsequent germline gene expression and/or genomic integrity.

Caenorhabditis elegans as a Useful Model for Studying Aging Mutations

“…The AMPK encoding gene is aak-2 in C. elegans . As a master regulator of cellular energy homeostasis, AMPK is required for the metabolic adjustment during the starved, developmentally quiescent diapause phase of C. elegans ( 69 ). The overexpression of AMPK extends lifespan, as shown in C. elegans ( 33 ).…”

“…Starvation can induce long-term consequences through epigenetic change. AMPK is required for metabolic adjustment by blocking specific chromatin modifications and epigenetic changes in C. elegans larvae to resist starvation ( 69 ). The recovery of C. elegans after starvation in the early larval stage would be impaired with the absence of AMPK, and could become sterile.…”

“…Greer et al demonstrated that deletion of the spr-5 in C. elegans causes a trans-generational increase in lifespan through mis-regulation and activation of lifespan-regulating signaling pathway ( 77 ). It is reported that SPR-5 has numerous consensus AMPK phosphorylation sites ( 69 ), but whether SPR-5 is yet another functional nuclear target of AMPK remains to be established.…”

The Review of Anti-aging Mechanism of Polyphenols on Caenorhabditis elegans

“…aak-2 is the encoding gene of AMPK in nematodes. AMPK is a regulator of cellular energy homeostasis, which is essential for the metabolic regulation of nematodes during starvation and diapause (Demoinet and Roy, 2018 ), it can be activated under low energy conditions and can maintain the steady state of energy, linking nutritional availability with longevity (Tullet, 2015 ). Overexpression of AAK-2 in nematodes prolongs its lifespan, and this effect also requires the downregulation of the IIS pathway and the upregulation and transposition of DAF-16 (Zhao et al, 2017 ).…”