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Quantitative Analysis of the Cellular Lipidome of Saccharomyces Cerevisiae Using Liquid Chromatography Coupled with Tandem Mass Spectrometry
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Mitochondrial membrane lipidome defines yeast longevity.

Adam Beach1, Vincent R Richard, Anna Leonov

  • 1Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada.

Aging
|August 9, 2013
PubMed
Summary

Lithocholic acid (LCA), a bile acid, significantly extends yeast lifespan by accumulating in mitochondria. This natural compound alters mitochondrial membranes, improving cellular functions and delaying aging.

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Area of Science:

  • Cellular Biology
  • Biochemistry
  • Aging Research

Background:

  • Bile acids, such as lithocholic acid (LCA), are increasingly recognized for their biological activities.
  • Caloric restriction (CR) is a known intervention that extends lifespan in various organisms.
  • The synergistic effects of LCA and CR on longevity require mechanistic elucidation.

Purpose of the Study:

  • To investigate the mechanism by which lithocholic acid (LCA) enhances the longevity-extending effects of caloric restriction (CR) in yeast.
  • To determine the localization and function of LCA within yeast cells under CR conditions.
  • To elucidate the role of mitochondrial membrane lipidome in LCA-mediated lifespan extension.

Main Methods:

  • Yeast cell culture under caloric restriction (CR) with and without exogenous lithocholic acid (LCA) addition.
  • Mitochondrial isolation and subfractionation to determine LCA localization.
  • Analysis of mitochondrial membrane lipidome composition, including glycerophospholipids.
  • Assessment of mitochondrial function: respiration, membrane potential, ATP synthesis, and reactive oxygen species (ROS) homeostasis.
  • Microscopy techniques to evaluate mitochondrial size, number, and morphology.

Main Results:

  • Lithocholic acid (LCA) enters yeast cells and localizes to both inner and outer mitochondrial membranes.
  • LCA induces significant age-related remodeling of mitochondrial glycerophospholipid synthesis and dynamics.
  • Alterations in mitochondrial membrane lipidome and morphology by LCA modulate mitochondrial respiration, membrane potential, ATP synthesis, and ROS homeostasis.
  • These LCA-induced changes in mitochondrial function synergize with CR to further extend chronological lifespan.

Conclusions:

  • Lithocholic acid (LCA) delays chronological aging in yeast by accumulating in mitochondrial membranes and altering their lipid composition.
  • Mitochondrial membrane lipidome plays a critical role in regulating yeast longevity.
  • LCA acts synergistically with caloric restriction (CR) to promote longevity through mitochondrial mechanisms.