# Molecular mechanisms of the mitochondrial permeability transition

> **NIH NIH R35** · NEW YORK UNIVERSITY · 2022 · $431,120

## Abstract

The overarching goal of my research program is to identify and characterize molecular mechanisms
responsible for stress-induced permeabilization of the mitochondrial inner membrane. In most eukaryotic
cells, mitochondria are the primary source of the energy that they provide in the form of ATP by
performing oxidative phosphorylation (OXPHOS). OXPHOS is a two-step process. First, substrate
oxidation by the respiratory chain results in the generation of the electrical potential on the mitochondrial
inner membrane. This potential energy drives generation of ATP by the phosphorylation of ADP at the
ATP synthase complex. To prevent energy dissipation and ensure that OXPHOS is efficient mitochondrial
inner membrane permeability should be tightly controlled and maintained at low levels. Stress conditions
associated with dysregulation of calcium and ROS homeostasis can lead to an increase in mitochondrial
inner membrane permeability – a phenomenon known as Mitochondrial Permeability Transition (mPT).
mPT causes dissipation of the membrane potential and loss of mitochondrial ATP-generating capacity
leading to cell dysfunction and death. mPT is critically involved in a broad spectrum of diseases ranging
from heart attack to neurodegeneration. Prevention of mPT is highly protective against cell death and
tissue damage suggesting high therapeutics potential. However, molecular mechanisms of mPT are not
well understood, and this gap in knowledge prevents mPT from being a drug target. Over the past five
years, we demonstrated that mPT is a multifaceted phenomenon and depending on the disease type and
stress severity, it can occur through different pathways. The central goal of our research program is to
identify the link between specific molecular mechanisms of mPT and specific stress conditions. We have
already established several original animal and cell disease-relevant models causing different types of
mPT. In our approach, a variety of methods that measure the mPT and tissue damage at the organismal,
cellular and mitochondrial levels are coupled with a number of our original electrophysiological (patch-
clamp) assays that allow direct measurement of mPT at the level of mitochondrial membranes and give
us a unique opportunity to dissect and characterize its multiple identities and regulation. The results of
our study will provide a detailed understanding of one of the most critical events in cell death cascades
and will bring an essential framework for the development of therapeutically approaches that will
selectively target mPT.

## Key facts

- **NIH application ID:** 10322360
- **Project number:** 5R35GM139615-02
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Evgeny Pavlov
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $431,120
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322360

## Citation

> US National Institutes of Health, RePORTER application 10322360, Molecular mechanisms of the mitochondrial permeability transition (5R35GM139615-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10322360. Licensed CC0.

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