# Role of CoQ in regulating thermogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $453,647

## Abstract

Project Summary
Coenzyme Q (CoQ, aka ubiquinone) is an important component of the mitochondrial
electron transport chain (ETC) as well as a membrane-incorporated antioxidant and a
co-factor for redox processes outside the mitochondria. CoQ deficiencies can be caused
by hereditary mutations in the biosynthesis pathway but are also associated with aging,
chronic diseases such as Type-2 Diabetes, and the pharmacological use of HMGCoA
inhibitors (statins). Due to the complexities of inter-organ communication, it has been
difficult to dissect the tissue specific effects of CoQ deficiencies and to identify primary
metabolic alterations. Since non-shivering thermogenesis heavily relies on mitochondrial
function and mitochondria-rich brown adipose tissue (BAT), we hypothesize that this
tissue will be disproportionately affected by CoQ deficiencies and have generated BAT
specific CoQ deficiency models both in vitro (pharmacological inhibition of CoQ
synthesis) and in vivo (UCP1-cre driven deletion of the CoQ biosynthetic enzyme
PDSS2). Indeed, we find that BAT CoQ deficiency from diminished de novo synthesis
within BAT results in tissue dysfunction and cold sensitivity. Interestingly, we find that the
primary mitochondrial defect in both pharmacological and genetic models of CoQ
deficiency appears not to be a decline in maximal mitochondrial respiration capacity but
a rapid down regulation of UCP1 expression and function. RNAseq data reveal a
transcriptional signature of CoQ deficiency in BAT that involves key regulators of the
mitochondrial unfolded protein response (UPRmt) and the integrated stress response
(ISR). We propose that activation of the IRS in BAT triggers metabolic adaptations
including decreased UCP1 expression and enhanced UCP1-independent
thermogenesis, in BAT and other tissues, via increased secretion of BAT para/autocrine
factors such as FGF21.

## Key facts

- **NIH application ID:** 10557141
- **Project number:** 5R01DK126830-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Andreas Stahl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $453,647
- **Award type:** 5
- **Project period:** 2021-02-26 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10557141

## Citation

> US National Institutes of Health, RePORTER application 10557141, Role of CoQ in regulating thermogenesis (5R01DK126830-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10557141. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*