# Investigation of compartmental PDHX during cellular senescence

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2021 · $68,562

## Abstract

INVESTIGATION OF COMPARTMENTAL PDHX IN CELLULAR SENESCENCE
The capacity to maintain homeostasis determines the overall health of the cell and the dysregulation of this
process can culminate into loss of cellular function and tissue deterioration ultimately leading to organismal
aging. Aging is a highly complex process with several distinct cellular hallmarks which include epigenetic
alteration, mitochondrial dysfunction, nutrient sensing, and cellular senescence. While these aging associated
biological processes are distinct, they are highly interconnected as the perturbation of one hallmark will affect
one or multiple other age-related processes. Cellular senescence, the process where a cell limits its proliferative
ability and ceases to divide is a hallmark of aging and implicated in age-related diseases. Senescent cells
undergo a rewiring of its chromatin landscape as well as its metabolism. While studies have addressed these
changes individually, few have examined the crosstalk of these metabolism and epigenetics in cellular
senescence. Metabolic enzymes and complexes have been known to regulate chromatin by providing pools of
metabolites that can be utilized by epigenetic enzymes for their catalytic activity. To uncover potential metabolic-
epigenetic axis in senescence, I performed a metabolic targeted CRISPR library screen in replicative
senescence and identified the deletion of Pyruvate Dehydrogenase Complex Component X (PDHX) delays
senescence. PDHX is a component of the pyruvate dehydrogenase complex and is primarily localized within the
mitochondria, however, we identified that a nuclear isoform is upregulated in senescence and PDHX increases
its association with chromatin during senescence. Immunoprecipitation of PDHX in the mitochondria as
compared to the nucleus indicates distinct protein interactions suggesting unique compartmental functions. Due
to the function of PDHX in metabolism and our preliminary data of its interaction on chromatin, we hypothesize
PDHX plays a key function in coordinating metabolism and chromatin dynamics required for cellular senescence.
Thus, the completion of the proposal will identify help elucidate a potential crosstalk between metabolism and
epigenetics in senescence and aging.

## Key facts

- **NIH application ID:** 10314664
- **Project number:** 1F32AG074641-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** KHOA ANH TRAN
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 1
- **Project period:** 2021-08-15 → 2022-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314664

## Citation

> US National Institutes of Health, RePORTER application 10314664, Investigation of compartmental PDHX during cellular senescence (1F32AG074641-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10314664. Licensed CC0.

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