# Mechanisms of Mitochondrial Degradation in Unstressed Mammalian Cells

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $376,950

## Abstract

Project Summary/Abstract
Mitochondria play essential roles in energy production and biosynthesis of a subset of macromolecules
necessary for eukaryotic life. They also house potentially dangerous intracellular machinery capable of
generating oxidative damage, triggering inflammatory signaling, and initiating programmed cell death.
Mitochondrial homeostasis is critical for maintaining a healthy pool of metabolically active mitochondria and
avoiding cellular damage caused by the accumulation of deteriorating mitochondria. One key component of
mitochondrial homeostasis is the selective degradation of old, damaged, or superfluous mitochondria. Recent
efforts have elucidated in great detail the molecular mechanisms through which experimentally damaged
mitochondria are degraded in Parkin-expressing eukaryotic cells. However, it is clear that mammalian cells also
undergo constant renewal of mitochondrial content through biogenesis of new mitochondria coupled to
degradation of old mitochondria, even in the absence of exogenous damage. The mechanisms controlling this
ongoing mitochondrial turnover are poorly understood. This proposal aims to illuminate the signal transduction
pathway that drives mitochondrial degradation in unstressed mammalian cells, and to use this pathway as an
entry point to understand the roles that basal mitochondrial degradation plays in cellular adaptation and stress
resistance. This will be accomplished by answering three key questions: 1) What controls the rate of
mitochondrial turnover in the absence of exogenous damage? 2) In the absence of exogenous damage, how
are mitochondria selected for degradation? 3) What role does this pathway play in developmentally programmed
mitochondrial clearance? These questions will be answered using molecular and genetic techniques on the
biochemical, cellular, and organismal scales. Answering these questions will provide substantial insights into
the mechanistic details and physiological roles of a fundamental cell biological process. This work will improve
understanding of normal development and homeostasis as well as the etiologies of diverse human diseases
against which mitochondrial homeostasis protects.

## Key facts

- **NIH application ID:** 9887587
- **Project number:** 1R01GM132231-01A1
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** MONDIRA KUNDU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,950
- **Award type:** 1
- **Project period:** 2020-03-10 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9887587

## Citation

> US National Institutes of Health, RePORTER application 9887587, Mechanisms of Mitochondrial Degradation in Unstressed Mammalian Cells (1R01GM132231-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9887587. Licensed CC0.

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