Petkevicius Group

Mitochondrial phospholipids: Understanding the regulation and the biological importance of mitochondrial phospholipid composition

Phospholipids are key components of cellular organelle membranes. Each cell contains thousands of unique phospholipid species, composed of different hydrophilic head groups and hydrophobic fatty acyl tails. Both the headgroup and the fatty acyl tail composition of cellular phospholipids affects the biophysical properties (fluidity, curvature, permeability) and the biological functions (signal transduction, transport, peroxidation) of cell membranes. Cellular phospholipid composition is altered in nearly all human diseases, as such, it is important to understand how cells sense and regulate their membrane phospholipid composition; to identify pathological states where altered cellular phospholipid composition plays a causal role in disease development and progression; and to investigate whether phospholipid composition can be pharmacologically corrected to treat disease.

Mitochondrial phospholipid metabolism predominantly takes place at the endoplasmic reticulum-mitochondria contact sites. These sites, termed mitochondria-associated membranes (MAMs), are where specific phospholipids from the endoplasmic reticulum are transferred to the mitochondria, as well as synthesized de novo from the phospholipid precursors. As such, both the outer and the inner mitochondrial membranes have distinct phospholipid compositions that are important for mitochondrial function. Our research aims to understand the biological mechanisms that regulate mitochondrial phospholipid acyl tail composition; how changes in acyl tail composition affect mitochondrial dynamics and functions; and how mitochondrial acyl composition is altered in various physiological and disease states. To address these questions, we use a combination of cell and molecular biology, lipidomics, lipid labelling and tracing, imaging and respirometry techniques.

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

Petkevicius K^#, Bidault G, Virtue S et al. (2021)
Macrophage beta2-adrenergic receptor is dispensable for the adipose tissue inflammation and function
Mol Metab 48:101220. doi: 10.1016/j.molmet.2021.101220
#co-corresponding author

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