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Updated: Sep 11, 2025
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Quantitative Analysis of the Cellular Lipidome of Saccharomyces Cerevisiae Using Liquid Chromatography Coupled with Tandem Mass Spectrometry
Published on: March 8, 2020
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Mitochondrial dysfunction and lipid dysregulation in yeast lacking phosphatidylserine
Alaumy Joshi1, Zakery N Baker2, Rachel A Stanfield1
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843.
Molecular Biology of the Cell
|August 13, 2025
Summary
Phosphatidylserine (PS) is crucial for mitochondrial function, impacting membrane potential and respiration. Yeast lacking PS show impaired bioenergetics and leaky membranes, revealing its essential role.
Area of Science:
- Cell Biology
- Biochemistry
- Mitochondrial Biology
Background:
- Mitochondrial phospholipids, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), are vital for mitochondrial structure and function.
- The specific roles of PC, PE, and CL are well-established, but the function of less abundant phosphatidylserine (PS) remains largely unknown.
Purpose of the Study:
- To investigate the role of phosphatidylserine (PS) in mitochondrial bioenergetics and lipid homeostasis.
- To engineer a yeast model system to study PS-deficient mitochondria, circumventing downstream lipid product interference.
Main Methods:
- Genetic and nutritional manipulation of yeast to create PS-lacking mutants.
- Exogenous ethanolamine supply to enable alternative biosynthesis of PE and PC.
- Mass spectrometry-based lipidomic analysis of cellular and mitochondrial lipids.
- Assessment of mitochondrial respiratory chain complex assembly and mitochondrial membrane potential.
Main Results:
- Mitochondrial respiration was impaired in PS-lacking yeast.
- PS deficiency led to loss of mitochondrial membrane potential and increased membrane permeability.
- No significant impact on the abundance or assembly of mitochondrial respiratory chain complexes was observed.
- An unexpected increase in odd-chain fatty acid-containing lipids was detected in PS-lacking cells.
Conclusions:
- Phosphatidylserine (PS) plays a critical, previously unrecognized role in maintaining mitochondrial membrane integrity and bioenergetic function.
- PS is essential for proper mitochondrial membrane biogenesis and bioenergetics.
- The study provides a valuable yeast system for further research into the cellular functions of PS.
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