Mitochondrial phospholipids: Understanding the regulation and the biological importance of mitochondrial phospholipid metabolism
Phospholipids are essential components of cellular organelle membranes, with each cell containing hundreds of unique phospholipid species that vary in their hydrophilic head groups and hydrophobic fatty acyl tails. The composition of these headgroups and fatty acyl tails influences the biophysical properties (e.g., fluidity, curvature, permeability) and biological functions (e.g., signal transduction, transport, peroxidation) of cell membranes. Since phospholipid composition is altered in nearly all human diseases, it is crucial to understand how cells sense and regulate their membrane phospholipid metabolism, as well as how changes in phospholipid composition contribute to disease onset and progression.
Beyond their well-known roles, mitochondria serve as central hubs for phospholipid biosynthesis. They synthesise key structural phospholipids for their own membranes and supply phospholipids or their precursors to other organelles. Our research focuses on understanding the regulation of mitochondrial phospholipid composition and the fates of mitochondria-derived phospholipids, such as phosphatidylglycerol, which is trafficked to lysosomes and converted into derivatives like bis(monoacylglycero)phosphate. To address these questions, we employ a combination of cell and molecular biology approaches, lipidomics, lipid labelling and tracing, protein purification, and in vitro enzymatic assays.
Biography
Kasparas Petkevicius [pɛt-kɛ:-vɪ-tʃus] holds a BSc degree in Biochemistry from the University of Bath (2013), with a one-year work placement at the MRC Protein Phosphorylation Unit in Dundee, Scotland. He then pursued a Wellcome Trust PhD Programme in Metabolic and Cardiovascular Disease at the Institute of Metabolic Science, University of Cambridge (2018), where he conducted his research in Antonio Vidal-Puig's group, investigating the role of adipose tissue macrophage lipid metabolism in obesity. Following the PhD, Kasparas joined AstraZeneca in Gothenburg, Sweden, as a postdoctoral fellow to study the biological importance of newly identified proteins that regulate cellular phospholipid composition. In 2021, he advanced to the role of Associate Principal Scientist at AstraZeneca, where he focused on early-stage drug discovery and target validation in metabolic disease. Kasparas took on an MRC 'Springboard to Independence' position at the MBU in April 2023, where he is leading an independent research programme on phospholipid metabolism in mitochondria.
Selected Publications
Sheokand PK, James AM, Jenkins B, K Lysyganicz P, Lacabanne D, King MS, Kunji ERS, Siniossoglou S, Koulman A, Murphy MP & Petkevicius K# (2025)
TRAM-LAG1-CLN8 family proteins are acyltransferases regulating phospholipid composition
Sci Adv 11(8):eadr3723. doi: 10.1126/sciadv.adr3723
#corresponding author
Petkevicius K#, Palmgren H, Glover MS et al. (2022)
TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
Nat Commun 13(1):6020. doi: 10.1038/s41467-022-33735-6
#corresponding author
Petkevicius K#, Virtue S, Bidault G et al. (2019)
Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity
Elife 8:e47990. doi: 10.7554/eLife.47990
#co-corresponding author
Palmgren H*, Petkevicius K*#, Bartesaghi S et al. (2022)
Elevated adipocyte membrane phospholipid saturation does not compromise Insulin signaling
Diabetes 29:db220293. doi: 10.2337/db22-0293
*co-first, #co-corresponding author
Petkevicius K#, Bidault G, Virtue S et al. (2021)
Norepinephrine promotes triglyceride storage in macrophages via beta2-adrenergic receptor activation
FASEB J 35(2):e21266. doi: 10.1096/fj.202001101R
#co-corresponding author