The Intrinsic Apoptosis Pathway Mediates the Pro-Longevity Response to Mitochondrial ROS in C. elegans

The Intrinsic Apoptosis Pathway Mediates the Pro-Longevity Response to Mitochondrial ROS in C. elegans

The oxidative theory of aging suggests that mitochondrial reactive oxygen species (mtROS) are generated by defective mitochondria. mtROS in turn can damage mitochondrial DNA (mtDNA), which causes more mtROS to be generated in a vicious cycle, compromising the bioenergetic capabilities of the affected tissue. This theory is attractive, as we do indeed observe an increase in mtROS in human aged tissues.

However two organisms, namely the nematode (C. elegans) and yeast (S. cerevisiae), force us to consider a more subtle picture. We observe mtROS signalling can in fact increase chronological lifespan in these organisms. The authors found that exposing C. elegans to low levels of the superoxide generator paraquat, generates a long-lived phenotype. They observed no difference in the pattern of cell death (apoptosis) during the development of the worms, however the activation of the biomolecular machinery of apoptosis was necessary to mediate the pro-survival signal. This suggests a novel role of the intrinsic apoptosis pathway in aging.

Hepatitis C Virus Triggers Mitochondrial Fission and Attenuates Apoptosis to Promote Viral Persistence

Hepatitis C Virus Triggers Mitochondrial Fission and Attenuates Apoptosis to Promote Viral Persistence

Mitophagy is a mitochondrial-recycling process, where defective mitochondria are targeted for removal and their components broken down for subsequent use by the cell. In this study, the authors show that HCV promotes fission of the mitochondrial network, followed by increased mitophagy, mediated by a protein called parkin. This in turn attenuates HCV-induced apoptosis, or cell death. They find that HCV induces Drp1 phosphorylation, which activates fission, and silencing Drp1 prevented HCV-induced fission and an increase in apoptotic signalling. This study demonstrates how a virus may take control of the bioenergetic infrastructure of a cell, to encourage its own persistence.