# Fis1 Regulation of Mitochondrial Fission

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $353,185

## Abstract

Project Summary/Abstract
 Altered division, or fission, of mitochondria has severe consequences even death. Yet the reasons for this
are unknown. It is postulated that the mitochondria have their own lifecycle that involves fission of unhealthy
mitochondria to remove them in an autophagic process called mitophagy. These quality control processes are
evolutionarily conserved between budding yeast and humans, although extent to which has recently been
called into question. In yeast, fission requires the protein FIS1 that is now thought to be dispensable for fission
in mammals, but indispensable for mitophagy. Consistent with this view are FIS1 interactions in mitophagy
human cell culture. Contrary to this view, loss of FIS1 elongates mitochondrial and displaces the fission
mechanoenzyme DRP1 from mitochondria in some, but not all, cell types. Mutations to some evolutionarily
conserved residues in FIS1 impair fission and DRP1 localization. Mutations to different conserved residues
impair binding to a critical adaptor in mitophagy, the Rab7 GTPase Activating Proteins TBC1D15 and
TBC1D17. These findings suggest that FIS1 is conserved for roles in both fission and mitophagy. Using yeast-
inspired mutations, along with state-of-the-art genetic, microscopic, and structural tools, we are now poised to
determine how conserved components govern the fate of mitochondria between fission, mitophagy, or
apoptosis. To understand the protein-protein interactions that govern this, biochemical and structural studies
will be integrated with state-of-the-art cell biological and genetic approaches. A better understanding of the
protein machinery and how it works will identify key points of regulation that may be targeted in future studies
with small molecules to inhibitor, and activate fission, mitophagy, and apoptosis. The discovery of such
molecules may ultimately lead to treatments for diseases in which enhanced, or impaired, fission activity is
central.

## Key facts

- **NIH application ID:** 10197141
- **Project number:** 5R01GM067180-17
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** R Blake Hill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $353,185
- **Award type:** 5
- **Project period:** 2004-01-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197141

## Citation

> US National Institutes of Health, RePORTER application 10197141, Fis1 Regulation of Mitochondrial Fission (5R01GM067180-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197141. Licensed CC0.

---

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