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.

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.

Mitochondrial dysfunction due to oxidative damage it has been linked to several pathological conditions, which has lead to an intense search for molecules with antioxidant properties at mitochondrial level. Avocado oil (AO) is a natural product that constitutes a source of lipophilic antioxidants. To evaluate the possible protective effects of AO against cellular and mitochondrial oxidative damage, we tested this oil in yeast cells subjected to oxidative stress induced by Fe2+. The growth of cell cultures in the presence of a quantity of AO equivalent to 10mM oleic acid increased cell viability in 36% and 11% after the exposure to 25 and 200 μM Fe2+, respectively. Avocado oil induced an increase of approximately 75% in both state 4 and uncoupled respiration at concentrations of Fe2+ up to 100 μM, while at 200 μM, respiration in uncoupled state was detected only in AO cells. No lipoperoxidation was detected at any condition studied. These results suggest that AO increase resistance of cells to oxidative stress by a lipoperoxidation‐independent mechanism by possibly increasing the respiratory capacity of the cell. This work was supported by CONACYT (130638 to CCR) and PROMEP (PTC‐266 to CCR) grants.