Interactions between oxygen homeostasis, food availability, and hydrogen sulfide signaling.

Nicole N Iranon,Dana L Miller

doi:10.3389/fgene.2012.00257

Abstract

The ability to sense and respond to stressful conditions is essential to maintain organismal homeostasis. It has long been recognized that stress response factors that improve survival in changing conditions can also influence longevity. In this review, we discuss different strategies used by animals in response to decreased O2 (hypoxia) to maintain O2 homeostasis, and consider interactions between hypoxia responses, nutritional status, and H2S signaling. O2 is an essential environmental nutrient for almost all metazoans as it plays a fundamental role in development and cellular metabolism. However, the physiological response(s) to hypoxia depend greatly on the amount of O2 available. Animals must sense declining O2 availability to coordinate fundamental metabolic and signaling pathways. It is not surprising that factors involved in the response to hypoxia are also involved in responding to other key environmental signals, particularly food availability. Recent studies in mammals have also shown that the small gaseous signaling molecule hydrogen sulfide (H2S) protects against cellular damage and death in hypoxia. These results suggest that H2S signaling also integrates with hypoxia response(s). Many of the signaling pathways that mediate the effects of hypoxia, food deprivation, and H2S signaling have also been implicated in the control of lifespan. Understanding how these pathways are coordinated therefore has the potential to reveal new cellular and organismal homeostatic mechanisms that contribute to longevity assurance in animals.

Highlights

All organisms must maintain homeostasis to survive
It is important to consider that it is experimentally difficult or impossible to separate damage that occurs in hypoxia or ischemia from effects that occur as a result of reoxygenation
C. elegans does not have a circulatory system, relying instead on diffusion for O2 delivery to cells. This allows for precise experimental control of both genotype and cellular environment (Shen and PowellCoffman, 2003; Fawcett et al, 2012). Because it is an attractive model for hypoxia research we have built a framework of hypoxia responses as a function of O2 tension using C. elegans, drawing connections with other systems when possible

Summary

Introduction

All organisms must maintain homeostasis to survive. Walter Cannon defined the modern concept of homeostasis as “the coordinated physiological reactions which maintain most of the steady states in the body. . ..” (Cannon, 1929). UPR activity is increased by decreased O2 in pancreatic β-cells and liver (but not cardiomyocytes), suggesting that it plays a conserved role in the cellular response to hypoxia (Tagliavacca et al, 2012; Zheng et al, 2012). Consistent with this, embryos do not require san-1, the spindle assembly checkpoint protein essential for suspended animation (Nystul and Roth, 2004), to survive exposure to hypoxia.

Results

Conclusion