The Funai laboratory is interested in the intracellular

fate of lipids into membrane phospholipids and how they affect cellular

energetics. In particular, mitochondrial membrane lipid composition becomes

robustly altered upon metabolic insults in multiple tissues. Genetic

disruptions or enhancements in pathways of mitochondrial phospholipid

biosynthesis are sufficient to recapitulate some of the physiological/pathological

phenotypes induced by such metabolic insults. Human mutations in the enzymes of

mitochondrial phospholipid biosynthesis cause severe mitochondrial defects and

are detrimental to health.

Mitochondrial lipid composition modulates the biophysical environment of the OXPHOS enzymes. Inner mitochondrial membrane is equipped with some of the enzymes of phospholipid biosynthesis thereby possessing an ability to self-regulate its lipid milieu. Both substrate availability and energy demand stimulate changes in mitochondrial membrane lipid composition. We believe that these changes drive the alterations in OXPHOS efficiency that lead to physiological adaptations or disease.

As a postdoctoral fellow in Clay Semenkovich’s lab, Katsu

developed a deep appreciation for subcellular lipid compartmentalization and

decided to pursue this topic when he started his laboratory in 2013. We first

characterized the relationship between mitochondrial lipidome and bioenergetics

in skeletal muscle (Heden et al., Sci Adv, 2019). We found that exercise and

physical inactivity robustly alter mitochondrial phosphatidylethanolamine (PE)

and described the role of this lipid in improving OXPHOS efficiency and driving

some of the physiological phenotypes associated with exercise or inactivity.

Leveraging this strategy, we are now beginning to implicate mitochondrial

lipids in other tissues such as adipose tissues, liver, pancreatic β cells, proximal tubules in the

kidney, etc. (Verkerke et al., Nat Metab, 2019; Johnson et al., Mol Metab, 2020;

Ferrara et al., biorχiv, 2022;

Siripoksup et al., biorχiv,

2022; Johnson et al., Sci Adv, 2023). Together, we hypothesize that

mitochondrial membrane lipids represent a common, fundamental mechanism by

which OXPHOS efficiency is altered to trigger metabolic diseases. In addition

to our studies in mitochondrial lipids, we have also studied ER phospholipids,

plasma membrane phospholipids, as well as lipid peroxidation. Our lab is

currently funded by grants from the National Institutes of Health and American

Heart Association.

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Eccles Institute of Human Genetics, Rooms 3440 and 3270

15 N 2030 E, Salt Lake City, Utah 84112