# Impact of mitochondrial structure on cellular homeostasis and hepatic injury

> **NIH NIH K99** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $89,880

## Abstract

Abstract:
In the cellular system, mitochondria form an intricate network of interconnected mitochondrion of
different shapes and sizes. The mitochondrion forms close contact with other cellular organelles
which are essential in maintaining the mitochondrial integrity as well as the functions. Emerging
evidence suggests the complexity of the mitochondrial architecture and processes involved in
the maintenance of functional mitochondrial pool in the cell. The mitochondrial architecture is
regulated by various pathophysiological signals like nutrient availability, hormonal regulation,
and stress conditions which regulates cytosolic calcium (cCa2+) dynamics as well. The dynamic
changes in the cCa2+ regulate mitochondrial shape through a Ca2+-sensing mitochondrial outer
membrane-anchored EF-hand containing protein Miro1. This phenomenon termed as the
mitochondrial shape transition (MiST) is independent of Miro1's role in mitochondrial trafficking
and Drp1-induced mitochondrial fission. Although Ca2+ signals fine-tune the mitochondrial
bioenergetic output, and sustained elevation of cCa2+ drives excessive mitochondrial Ca2+
uptake which is a prerequisite for the opening of mitochondrial permeability transition pore
(MPTP), mitochondrial swelling, plasma membrane rupture, and necrotic cell death. Preliminary
data suggest that in response to MiST, endoplasmic reticulum (ER)-mitochondrial tethering is
increased which may be essential for both MPTP opening and the mitophagic response. In
response to hepatic ischemia-reperfusion injury (IRI), MPTP opening leads to the onset of
hepatic necrosis and subsequent organ failure. Mitochondrial integrity is crucial for hepatic
function and survival after IRI. However, the underlying molecular mechanism for the
maintenance of mitochondrial integrity is largely unidentified. Therefore,we will mechanistically
examinethe link betweenMiST, MPTP, and mitophagy with a particular emphasis on the role of
Miro1 in MPTP formation, initiation of mitophagy, and induction of necrosis in response to the
hepatic IRI. The project outline will enable the development of essential skills and expertise
needed to develop PI's independent research program focusing on the mitochondrial biology in
the hepatic system.

## Key facts

- **NIH application ID:** 10116370
- **Project number:** 5K99DK120876-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Dhanendra Tomar
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $89,880
- **Award type:** 5
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116370

## Citation

> US National Institutes of Health, RePORTER application 10116370, Impact of mitochondrial structure on cellular homeostasis and hepatic injury (5K99DK120876-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10116370. Licensed CC0.

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