# Molecular composition of the mitochondrial permeability transition pore

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2020 · $339,844

## Abstract

Mitochondrial Permeability Transition Pore (mPTP) is a large non-selective channel located in the
mitochondrial inner membrane. It has been established that prolonged opening of mPTP during stress
conditions leads to the increase in permeability of the mitochondrial membrane, disruption of energy
generation in the form of ATP and eventually to cell death. mPTP opening is the central event leading
to tissue damage during stroke. Thus, block of mPTP by pharmacological agents can be highly
protective. However, current knowledge of the molecular composition of the channel (“pore”) part of
mPTP remains incomplete. The central goal of the current proposal is to test the hypothesis that
formation of the functional conducting channel of the mPTP requires the presence of non-
proteinaceous polymers of inorganic polyphosphate and polyhydroxybutyrate in combination with the C-
subunit and Ca2+. Experiments will involve use of several approaches. First, we will use
electrophysiology to study the activity of the purified mPTP channel. Next, we will investigate the
molecular composition and assembly of mPTP by using a number of analytical approaches including
immunochemistry and mass spectroscopy. Finally, we will use wild-type and genetically modified
cultured neurons and stable cell lines to investigate interactions between C-subunit, polyphosphate and
polyhydroxybutyrate during mPTP activation in living cells. We expect that results of our study will lead
to the detailed understanding of one of the most fundamental and critical molecular processes during
cell death. In the future, this new knowledge will open opportunities for novel treatment strategies,
which will specifically target these non-proteinaceous components of the pore, effectively prevent
mPTP opening and protect against tissue damage.

## Key facts

- **NIH application ID:** 10004077
- **Project number:** 5R01GM115570-05
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Evgeny Pavlov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,844
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004077

## Citation

> US National Institutes of Health, RePORTER application 10004077, Molecular composition of the mitochondrial permeability transition pore (5R01GM115570-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10004077. Licensed CC0.

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