Funai Lab

Research Overview

Since 2013, my laboratory has been interested in the intracellular fate of lipids into membrane phospholipids and how they affect cellular metabolism. This was driven by my curiosity to understand how lipids mediate obesity-driven metabolic diseases.

We have studied and published on ER (Funai et al., JCI, 2013; Paran et al., Obesity, 2015; Funai et al., Diabetes, 2016; Verkerke et al., Nature Metabolism, 2019) and plasma membrane phospholipids (Ferrera et al., JCI, 2021; Ferrera et al., FASEB J, 2021). However, we have extensively published and developed reputation on understanding how mitochondrial membrane phospholipids influence bioenergetics to alter propensity for metabolic diseases (Heden et al., Trends Endo Metab, 2016; Johnson et al., J Mol Cell Cardiol, 2018; Heden et al., Science Advances, 2019; Johnson et al., Mol Metab, 2020; Funai et al., Curr Opin Cell Biol, 2020; Johnson et al., Science Advances, 2023; Ferrara et al., Life Metab, 2023; Siripoksup et al., JCI, 2024; Decker et al., Cell Metabolism, 2024; Brothwell et al., eLife, 2025). In this line of work, we have been examining how mitochondrial membrane lipids alter with changes in energy supply or demand in different tissues, and implicate their roles in bioenergetics and metabolic physiology.

As described below, our lab continues to work in this area with new emphasis on addressing more fundamental and mechanistic questions about how mitochondrial lipids influence bioenergetics. We have two additional major lines of research in my laboratory:

  • The role that lipid peroxidation plays in skeletal muscle mass and function
  • The mechanisms and physiological implications that drive an increase in mitochondrial energy efficiency after weight loss

All of these topics synergize with our expertise and interests in mitochondrial bioenergetics, lipid metabolism, endocrinology, exercise physiology, skeletal muscle biology, and mass spectrometry.

We are also expanding our research beyond understanding the mechanisms and have started or are in the process of starting clinical studies/trials to test our findings in humans.

Current Research Areas

Mitochondrial Membrane Lipids and Energy Flux through OXPHOS

We investigate how mitochondrial membrane lipids regulate energy metabolism by their influence on oxidative phosphorylation. Using high-resolution respirometry and fluorometry, we study the influence of lipids on the energy-transducing steps of oxidative phosphorylation in various tissues and disease states.

Lipid Peroxidation and Carbonyl Stress

We study how lipid peroxidation contributes to decline in muscle function with aging, disuse, and cancer. Our ongoing work focuses on testing histidine-containing dipeptides as means to neutralize reactive lipid byproducts, with clinical trials testing efficacy to ameliorate muscle dysfunction. We are also developing new mass spectrometry methods to understand how lipids covalently modify the cellular proteome to promote tissue dysfunction.

Semaglutide-Induced Weight Loss and Skeletal Muscle Mitochondrial Energy Efficiency

We discovered that weight loss, induced by either diet or incretin mimetics such as semaglutide, increases skeletal muscle mitochondrial energy efficiency. These observations may explain the reduced energy expenditure that is known to occur after weight loss. We are interested in molecular mechanisms by which weight loss increases the efficiency of ATP synthesis by skeletal muscle mitochondria.