# Cyclophilin D Regulates Neonatal Cardiac Bioenergetics and Function

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $505,474

## Abstract

Birth is the most abrupt transition during life, and the neonatal heart must accommodate to this dramatic
change in environment by increasing its output to the body. Exposure to higher levels of oxygen at birth likely
activates intracellular pathways that allow cardiac myocytes to rapidly proliferate and then differentiate to
cause the final maturation of cardiac structure and function that is required for this increased output and
survival. However, major gaps in our understanding of this process remain.
 It is apparent that mitochondria play an important role in this process. We have found that mitochondria
regulate cardiac development in the embryo and neonate and that the mitochondrial chaperone protein,
cyclophilin D (CyPD), regulates changes in mitochondrial function and reactive oxygen species (ROS)
production that control cardiomyocyte proliferation and differentiation. Our preliminary data have begun to
define changes in this CyPD-mitochondrial-ROS-differentiation pathway that occur in the neonatal heart. In
addition, these data provide novel models to dissect the mechanisms of this pathway.
 These findings suggest the hypothesis that increased O2 at birth initiates a rise and then fall in CyPD
activity, which regulates mitochondrial function, particularly ROS production, to control neonatal myocyte
proliferation and differentiation and cardiac function. The scientific premise of this proposal is supported by
data discussed above, but the mechanisms involved have not been fully elucidated. Our overall goal is to use
our expertise in cardiac development and mitochondrial biology to dissect the mechanisms that control this
important physiologic pathway in the neonatal heart and determine if CyPD inhibition can be used to
ameliorate pathology in clinically relevant models. To achieve these goals, we propose 3 Specific Aims: 1.
Determine how CyPD controls the neonatal cardiac mitochondrial-ROS-differentiation pathway. 2. Determine
effects of disrupting CyPD activity in the neonatal heart. 3. Determine effects of hypoxia on the neonatal CyPD-
mitochondria-ROS-differentiation pathway.
 The proposed experiments use a novel set of pharmacologic and genetic approaches that manipulate
oxygen, CyPD, inner mitochondrial membrane coupling, and ROS in the neonatal heart. Specimens will be
processed using a battery of assays to measure CyPD expression, acetylation, and activity; mitochondrial
structure and function, ETC activity and assembly, ROS production; myocyte proliferation and differentiation;
and cardiac function. Our team has unique expertise in cardiac, developmental, and mitochondrial biology and
in biostatistics and we employ novel concepts and cutting-edge techniques to study mitochondria during late
cardiac development. The anticipated results will significantly change our understanding of bioenergetics in the
neonatal heart and will lead to future studies that use mitochondrial targeted therapies to enhance cardiac
function and cardiac m...

## Key facts

- **NIH application ID:** 10242768
- **Project number:** 5R01HL144776-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** George A Porter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $505,474
- **Award type:** 5
- **Project period:** 2019-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242768

## Citation

> US National Institutes of Health, RePORTER application 10242768, Cyclophilin D Regulates Neonatal Cardiac Bioenergetics and Function (5R01HL144776-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242768. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*