Mechanisms Underlying the Essential Role of Mitochondrial Membrane Lipids in Yeast Chronological Aging

Abstract

The functional state of mitochondria is vital to cellular and organismal aging in eukaryotes across phyla. Studies in the yeast Saccharomyces cerevisiae have provided evidence that age-related changes in some aspects of mitochondrial functionality can create certain molecular signals. These signals can then define the rate of cellular aging by altering unidirectional and bidirectional communications between mitochondria and other organelles. Several aspects of mitochondrial functionality are known to impact the replicative and/or chronological modes of yeast aging. They include mitochondrial electron transport, membrane potential, reactive oxygen species, and protein synthesis and proteostasis, as well as mitochondrial synthesis of iron-sulfur clusters, amino acids, and NADPH. Our recent findings have revealed that the composition of mitochondrial membrane lipids is one of the key aspects of mitochondrial functionality affecting yeast chronological aging. We demonstrated that exogenously added lithocholic bile acid can delay chronological aging in yeast because it elicits specific changes in mitochondrial membrane lipids. These changes allow mitochondria to operate as signaling platforms that delay yeast chronological aging by orchestrating an institution and maintenance of a distinct cellular pattern. In this review, we discuss molecular and cellular mechanisms underlying the essential role of mitochondrial membrane lipids in yeast chronological aging.

Lipid metabolism and transport define longevity of the yeast Saccharomyces cerevisiae

“…A body of evidence supports the notion that LCA slows down yeast chronological aging because it instigates specific changes in the concentrations of mitochondrial membrane phospholipids (178-183). This evidence has recently been thoroughly discussed (184)(185)(186)(187)(188). We therefore briefly summarize below the data confirming that certain LCA-dependent changes in mitochondrial membrane phospholipids play essential roles in the ability of LCA to extend yeast CLS.…”

Caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of a quiescent state, entry into a non-quiescent state and survival in the non-quiescent state

“…Recent studies have revealed that the longevity-extending effect of CR in chronologically aging yeast depends on the cellular homeostasis of two classes of lipids, namely triacylglycerols (TAG) and cardiolipins (CL) [ 2 , 4 , 122 - 135 ]. TAG are so-called neutral lipids that in yeast are synthesized in the endoplasmic reticulum and then deposited in lipid droplets to serve as the main storage molecules for maintaining energy homeostasis and supplying free fatty acids [ 136 - 139 ], whereas CL are signature lipids of the inner mitochondrial membrane implicated in oxidative phosphorylation and several other vital processes confined to mitochondria [ 140 - 143 ].…”

Anhydrobiosis in Yeasts: Changes in Mitochondrial Membranes Improve the Resistance of Saccharomyces cerevisiae Cells to Dehydration–Rehydration

“…In this series of experiments, we again used the dehydration resistant yeast S. cerevisiae 77, two concentrations of DMSO (0.05% and 1%), and two concentrations of LCA (50 μM and 100 μM). LCA concentrations in these experiments were selected according to the results of Dr. V.I.Titorenko group (38)(39)(40)(41). It is necessary to mention here that in this and in the next series of experiments we artificially decreased the viability of dehydrated cells of S. cerevisiae 77 comparing it with usual high viability of dehydrated cells of this strain which was obtained also in the studies described above (Figure 1).…”

“…These experiments were carried out using S. cerevisiae 14, which is only moderately resistant to dehydration-rehydration treatments. In these experiments, we attempted to determine if LCA stabilizes the plasma membrane, along with making the previously described changes to lipids in the mitochondrial membranes [38][39][40][41]. To do this we measured changes in the permeability of the plasma membrane.…”

“…This enables the mitochondria to operate as signaling organelles that orchestrate an establishment of an anti-aging transcriptional program for many longevity-defining nuclear genes. LCA also alters numerous proteins in cellular locations outside of the mitochondria [40,41]. On the basis of these studies, we attempted to determine if the external addition of LCA to yeast cells would be essential for the stability of cells during the dehydration-rehydration process.…”