# Mitochondrial Biogenesis in Kidney Disease

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $466,109

## Abstract

PROJECT SUMMARY
Acute kidney injury (AKI) is a growing public health burden. The syndrome itself is occurring in more diverse
contexts and the long-term sequelae of AKI include chronic kidney disease (CKD). More than ever then, AKI
research must identify candidate pathways that can be assessed and targeted in humans. In the first four years
of this award, the applicant's laboratory has found that the mitochondrial biogenesis regulator, PGC1α
(PPARγ-coactivator-1α), confers robust resistance to simple, common acute stressors that culminate in AKI
such as acute systemic inflammation and renal ischemia. Moreover, we have observed that renal PGC1α
expression is markedly suppressed in human AKI. Finally, we have implicated a novel downstream effector
pathway for PGC1α—biosynthesis of the energy carrier nicotinamide adenine dinucleotide (NAD+). Based
upon these results, we hypothesize that the PGC1α-NAD+ pathway may be a critical determinant of metabolic
defense against diverse renal tubular insults. To test this concept in ways that advance both our fundamental
understanding of this emerging candidate and that catalyze translational efforts, we propose three parallel
aims: (1) identify when in the CKD-AKI spectrum tubular PGC1α induction is most beneficial; (2) critically
evaluate the role of NAD+ biosynthetic pathways in experimental AKI downstream of PGC1α; and (3) dissect
the relative contributions of mitochondrial biogenesis versus NAD+ biosynthesis in the metabolic protection
conferred by PGC1α. To accomplish this, our team is composed of individuals possessing complementary
expertise with a proven track record of collaborating to investigate metabolism in AKI. We have developed a
suite of tools ranging from metabolomics and lipidomics applications to gene-edited cells to function-
ultrastructure analysis of mitochondria. The output from the proposed aims will advance our understanding of
how renal tubular metabolism bridges CKD and AKI; identify specific contexts in which PGC1α-NAD+ should
be pursued clinically; and deepen our fundamental understanding of PGC1α and NAD+ in renal health. In
concert with a growing number of outstanding groups investigating renal metabolism, it is our hope that the
proposed studies help expand this new frontier in renal biology.

## Key facts

- **NIH application ID:** 10062945
- **Project number:** 5R01DK095072-08
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Samir M Parikh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,109
- **Award type:** 5
- **Project period:** 2012-09-27 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062945

## Citation

> US National Institutes of Health, RePORTER application 10062945, Mitochondrial Biogenesis in Kidney Disease (5R01DK095072-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10062945. Licensed CC0.

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