ABSTRACT
Potential targets of oxidative damage in the cell have recently been reviewed (Figure 12.1) (Murphy et al., 2011; Murphy, 2009). For many years it was widely accepted that a major pathway for amplifying reactive oxygen species (ROS)- mediated damage causing aging involves a mechanism in which ROS act directly to mutagenize mtDNA. ROS, such as generated by mitochondria, were envisioned to directly attack the bases of mtDNA-generating mutations, thus causing aging. Recent data suggest that errors of replication of mtDNA, not ROS, generate mutations that cause aging (see Chapter 9). These data open Pandora’s box concerning what fundamental roles, if any, oxidative stress mediated by ROS plays in aging. The purpose of this chapter is to make a single point-membranes deserve more attention as mediators of aging. Case histories are chosen to document that membranes are clearly major targets of oxidative damage. We suggest that mitochondrial membranes of humans belong to a class of specialized membranes sensitive to peroxidation; the result is a membrane dysfunction so powerful as to trigger apoptosis.
