# Mitochondrial Therapy for Kidney Injury

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $346,500

## Abstract

Project Summary or Abstract
 Prevention and treatment of acute kidney injury (AKI) continues to remain a significant health problem.
Considerable data suggest that the immune system mediates AKI, and development of anti-inflammatory
treatments can significantly attenuate tissue injury and loss of function. However, the side effects of common
anti-inflammatory therapies combined with the lack of clinical data, supporting the involvement of the immune
system in AKI pathogenesis, have hindered the development of anti-inflammatory options. Mitochondria,
critical players in AKI, have dual roles as a primary source of energy (ATP) and as key regulators of cell death.
Renal ischemia followed by reperfusion (IRI) induces mitochondrial fragmentation in 30-40% of proximal tubule
(PT) cells along with reduced expression of the mitochondrial biogenesis regulator, PGC1 (PPARγ-
coactivator 1). Systemic intravenous injection of fluorochrome labeled isolated healthy mitochondria signal is
found in various tissue including spleen, kidneys, liver and lungs as early as 15 mins after injection. In kidneys
the isolated labeled mitochondria are predominantly taken up by PT. Our preliminary studies demonstrate a
potential therapeutic role for healthy mitochondria isolated from a healthy source (muscle or liver) to alter
immune and kidney resident cellular responses to prevent injury (pretreatment) and induce recovery (post-
treatment) that may involve activation of recipient mitochondria biogenesis through induction of PGC1α. The
transferred mitochondria 1) enhance ATP production and oxygen consumption rate of recipient cell, 2) localize
to the kidneys, 3) reduce inflammatory responses (cell death, cytokines, inflammatory cell infiltration), and 4)
induce recipient cell PGC1, a pivotal determinant of renal responses, to protect kidneys from AKI.
 Therefore, direct mitochondrial transfer as a therapeutic intervention to repair, reprogram and replace
mitochondria, improve mitochondrial health and restore respiratory function is beneficial for prevention and/or
treatment of disease. Accordingly, we hypothesize that treatment with healthy mitochondria enhances
recipient cell energy production to help replace damaged mitochondria by inducing PGC1α and rescues
cellular functions. We will test our hypothesis with the following three aims: Aim 1: To test the hypothesis that
treatment with isolated healthy mitochondria helps maintain cellular functions to block (pretreatment) AKI and
prevent (post-treatment) progression of disease in two models (IRI and LPS-induced sepsis) of AKI in mice.
Aim 2: To test the hypothesis that uptake of healthy mitochondria induces the mitochondrial metabolism gene
(PGC1α) to increase mitochondrial numbers and intracellular ATP to protect from AKI. Aim 3: To test the
hypothesis that treatment with isolated mitochondria helps maintain cellular functions in larger animals (swine)
to protect kidneys from IRI.

## Key facts

- **NIH application ID:** 10188518
- **Project number:** 5R01DK117183-05
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Amandeep Bajwa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,500
- **Award type:** 5
- **Project period:** 2018-09-22 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188518

## Citation

> US National Institutes of Health, RePORTER application 10188518, Mitochondrial Therapy for Kidney Injury (5R01DK117183-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10188518. Licensed CC0.

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