Live longer on MARS: a yeast paradigm of mitochondrial adaptive ROS signaling in aging

Abstract

Adaptive responses to stress, including hormesis, have been implicated in longevity, but their mechanisms and outcomes are not fully understood. Here, I briefly summarize a longevity mechanism elucidated in the budding yeast chronological lifespan model by which Mitochondrial Adaptive ROS Signaling (MARS) promotes beneficial epigenetic and metabolic remodeling. The potential relevance of MARS to the human disease Ataxia-Telangiectasia and as a potential anti-aging target is discussed.

Keywords: aging; ataxia-telangiectasia; epigenetic; hormesis; mitochondria; reactive oxygen species; signaling.

Figure 1. FIGURE 1: Mitochondrial Adaptive ROS Signaling (MARS).

Depicted at the top are ROS (superoxide and hydrogen peroxide) generated in various mitochondrial subcompartments, and, in the case of hydrogen peroxide, possibly crossing membranes to signal directly in the cytoplasm. I propose that there are mitochondrial ROS sensors associated with mitochondria that can directly be modified by ROS or in the cytoplasm that can detect some ROS-dependent second messenger from mitochondria. MARS signals are then relayed to other cellular compartments by redox-sensitive kinases or other effectors. The end result is an adaptive change that can have a beneficial effect on cellular homeostasis and survival. To the right is the budding yeast MARS paradigm, based on CLS extension in response to reduced TORC1 signaling as described in the text. Specific known components and outcomes of yeast MARS system are shown. The question mark denotes an important gap in knowledge, which is the nature of precise mitochondrial ROS-dependent signals and sensors. A generalized MARS scheme is depicted on the left.