Increased membrane unsaturation has been associated with shorter longevity due to higher sensitivity to lipid peroxidation (LP) leading to enhanced mitochondrial dysfunction and ROS overproduction. However, the role of LP during aging has been put in doubt along with the participation of electron leak at the electron transport chain (ETC) in ROS generation in aged organisms. Thus, to test these hypothesis and gain further information about how minimizing LP preserves ETC function during aging, we studied the effects of α-linolenic acid (C18:3) on in situ mitochondrial ETC function, ROS production and viability of chronologically aged cells of S. cerevisiae, whose membranes are intrinsically resistant to LP due to the lack of PUFA. Increased sensitivity to LP was observed in cells cultured with C18:3 at 6 days of aging. This was associated with higher viability loss, dissipated membrane potential, impaired respiration and increased ROS generation, being these effects more evident at 28 days. However, at this point, lower sensitivity to LP was observed without changes in the membrane content of C18:3, suggesting the activation of a mechanism counteracting LP. The cells without C18:3 display better viability and mitochondrial functionality with lower ROS generation even at 28 days of aging and this was attributed to full preservation of complex III activity. These results indicate that the presence of PUFA in membranes enhances ETC dysfunction and electron leak and suggest that complex III is crucial to preserve membrane potential and to maintain a low rate of ROS production during aging.

The importance of the unsaturation degree of fatty acids (FA) from mitochondrial membranes in aging has been exposed by an inverse correlation between the aging rate of several species and the unsaturation degree of its membrane FA and peroxidation sensitivity. Although S. cerevisiae has been accepted as a model for the study of the molecular mechanism involved in aging, it can yield limited information about the role of FA in aging because of its membrane FA composition, which consists of FA resistant to peroxidation. To address this issue, we have studied the effects of linolenic acid (C18:3) in yeast chronological aging and mitochondria function. C18:3 decreased in > 50% the cell viability at 6 days of cultivation while almost completely abolished viability at 28 days. This was consistent with a decrease of > 60% in the activity of complexes II and III in C18:3 cells of any age. No mitochondrial membrane potential and loss of respiratory capacity were observed in 28‐days cells with C18:3. These results suggest that native fatty acids of yeast extend its longevity by preserving mitochondrial functions related with energy metabolism. This work was supported by a CONACYT grant (130638 to CCR)

Correlative evidence from comparative studies has suggested that longevity in higher eucaryotes keeps an inverse correlation with the unsaturation degree of mitochondrial membranes. Since lipid peroxidation (LP) depends on the number of double bonds, it has been hypothesized that lower unsaturation degree of the membranes from longevous animals preserves mitochondrial function from the damage by ROS. To further test this hypothesis, we have studied if accelerated aging and impaired mitochondrial function by the incorporation of PUFA in the yeast is associated with increased sensitivity to LP and enhanced ROS production. When yeast incorporated C18:3 into mitochondrial membranes, it was observed accelerated aging along with increased ROS production, which was attributed to impairment in electron transfer between complex II and complex III. These effects were associated with a higher susceptibility to LP, although the cells become more resistant to this process at late stages of aging. These data confirm the observations made in higher eukaryotes about the primordial role of LP in the mitochondrial impairment associated to a lower longevity. This work was funded by a CONACYT (130638 to CCR) grant.