# Mulan: a novel regulator of mitochondrial dynamics, mitophagy and heart function

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $678,860

## Abstract

PROJECT SUMMARY .
Mitochondria play a pivotal role in regulating cardiac function in health and disease by
regulating energy balance, biosynthetic processes, and cellular survival. Mitochondrial quality
control and homeostasis are maintained in part through fusion and fission of mitochondria as
well as through autophagic clearance or mitophagy of damaged mitochondria. Disruption of
mitochondrial homeostasis has been closely linked to a host of acquired and genetic disease
states, characterized by cardiomyocyte death at the cell level and overt cardiac dysfunction at
a systemic level. Thus, clearly a thorough understanding of the molecular regulators of
mitochondrial homeostasis in the heart is critical for reducing cardiac dysfunction related
mortality. Our preliminary data demonstrate that the mitochondrial E3 ubiquitin ligase, Mulan,
is a novel regulator of mitochondrial dynamics and mitophagy in mammalian hearts. Mulan
participates in the maintenance of mitochondrial integrity and function. While Parkin, a
cytoplasmic E3 ligase, has been extensively studied in mitophagy, Mulan's proposed role as a
mitochondrial injury sensor, mediator of mitophagy, and inducer of cell death is both novel
and a significant departure from the current state of understanding in the field. Given that
Mulan is upregulated in Parkin null mouse hearts, we postulate that Mulan's upregulation may
serve to compensate for the loss of Parkin, thus maintaining the basal cardiac function of
Parkin null mice. Employing state-of-the-art techniques, we will investigate the intricacies of
protein-protein and protein-substrate interactions by Mulan as well as how modulation of
Mulan's expression fundamentally alters mitochondrial dynamics. Ultimately, our data may
provide the first glimpse of an unrecognized, yet significant role of Mulan as a “resident
mitochondrial injury-sensor” in the heart. Furthermore, we intend to define the distinct
contribution of Mulan in mitophagy, that is independent from Parkin, as well as Mulan's role in
mitochondrial function, dynamics, and cell death in the heart. Given the emerging importance
of mitochondrial dysfunction in cardiac pathology, the findings from our proposal will help
define the role of Mulan as a key mitochondrial injury-sensor. In addition, the proposed
studies will have broad implications for the understanding and treatment of heart disease.

## Key facts

- **NIH application ID:** 9889167
- **Project number:** 5R01HL132511-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ronglih Liao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $678,860
- **Award type:** 5
- **Project period:** 2017-02-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889167

## Citation

> US National Institutes of Health, RePORTER application 9889167, Mulan: a novel regulator of mitochondrial dynamics, mitophagy and heart function (5R01HL132511-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9889167. Licensed CC0.

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