The search for nonconventional mitochondrial determinants of aging

Abstract

Mitochondria are conventionally believed to modulate aging by affecting free-radical production and the energy supply. In this issue of Molecular Cell, Caballero et al. (2011) reveal that altering protein complexes involved in mitochondrial translation control extends life span independent of redox homeostasis and oxidative phosphorylation.

Figure 1. Disruption of specific components in the mitochondrial translational control (MTC) complexes extends the replicative lifespan in yeast

Mss51 is required both for translation of the COX1 mRNA and for Cox1 assembly. Pet309 is also required for translation of the COX1 mRNA as well as for the stability of intron-containing transcripts. Sov1 controls the stability of the VAR1 mRNA. Cbs1, Cbs2 and Cbp6 are involved in the translation of the cytochrome b (COB) mRNA. These three proteins form a membrane-tethered supercomplex with the 5′-end processing factor, Cbp1, and the mitochondrial transcriptional machinery comprising Rpo41 and Nam1. Aep1 and Aep2 are required for the stability and expression of the ATP9 mRNA. Pet127 is a 5′-to-3′ exoribonuclease involved in the 5′-end processing of several transcripts. Dss1 and Suv3 form the ATP-dependent 3′-to-5′ exoribonuclease for RNA turnover, processing and surveillance. Proteins whose loss extends lifespan (Caballero et al., in press; Heeren et al., 2009) are highlighted in red. Pet309, Cbs1, Pet127 and probably also Cbp6 are associated with the inner membrane. Whether Sov1, Aep1, Dss1 and Suv3 are associated with the membrane is less clear. The black question mark denotes an as yet unknown mitochondrial signal elicited by alterations to the MTC complexes. IM, inner membrane; OM, outer membrane; IMS, intermembrane space.