# Regulation of Mitochondrial Biogenesis and Function by DsbA-L in the Liver

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $339,818

## Abstract

Abstract
Mitochondria in hepatocytes play a major role in maintaining whole-body energy metabolism and normal
function of the liver. Impaired mitochondrial function is closely associated with various metabolic diseases such
as obesity, insulin resistance, and hepatosteatosis. However, the precise underlying mechanisms remain to be
fully elucidated. Filling this major gap of knowledge will yield new information on the mechanisms underlying
mitochondrial dysfunction-associated liver diseases, insulin resistance, and type 2 diabetes.
Our current study focuses on the functional roles and mechanisms of action of the disulfide-bond-A
oxidoreductase-like protein (DsbA-L). We recently found that DsbA-L expression is significantly reduced in the
liver of obese human subjects and diet-induced obese mice. In addition, loss- and gain-of-function studies
reveal that DsbA-L is a key regulator of mitochondrial integrity and function and its deficiency in the liver plays
an important role in obesity-induced hepatosteatosis and metabolic dysfunction. In the current study, we will use
molecular and cellular approaches as well as knockout animal models to elucidate the mechanisms regulating
mitochondrial integrity and function under physiological and pathophysiological conditions. This research should
shed new light on the link between obesity, mitochondrial impairment, and liver dysfunction and further our
understanding of the mechanisms underlying obesity-induced insulin resistance and metabolic diseases. Thus,
our proposed studies should provide valuable information on the biology of DsbA-L potentially being useful as
targets of anti-obesity and anti-insulin resistance therapeutics.

## Key facts

- **NIH application ID:** 10251019
- **Project number:** 5R01DK114479-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** ALAN FRAZER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,818
- **Award type:** 5
- **Project period:** 2018-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251019

## Citation

> US National Institutes of Health, RePORTER application 10251019, Regulation of Mitochondrial Biogenesis and Function by DsbA-L in the Liver (5R01DK114479-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10251019. Licensed CC0.

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