Research Perspective Volume 2, Issue 12 pp 1004—1011

Figure 1. Opposing effects of prohibitin deficiency on aging. Under normal conditions prohibitin promotes survival by moderating fat metabolism, mitochondrial proliferation and function, as well as, energy and ROS levels. In wild type animals, elimination of prohibitin results in mitochondrial defects and elicits a retrograde cellular response leading to mitochondria overproliferation and altered fat metabolism. In turn, accumulation of defective mitochondria lacking prohibitin results in increased reactive oxygen species production, metabolic defects, consequent cellular damage and reduced lifespan. Under reduced diapause signaling or under stress, where AKT/SGK-mediated inhibition of DAF-16/FOXO nuclear localization is relieved and stress kinases (AMPK, JNK) are activated, mitochondrial overproliferation is inhibited and cellular metabolism is adjusted towards fat utilization, promoting longevity.