Date of Degree
PhD (Doctor of Philosophy)
Grueter, Chad E.
First Committee Member
Abel, Dale E.
Second Committee Member
Third Committee Member
Fourth Committee Member
Fifth Committee Member
Although pathological alterations in gene expression and mitochondria function in response to cardiac ischemia are well recognized, the mechanisms driving these changes are incompletely understood. Nuclear to mitochondrial communication regulating gene expression and mitochondrial function is a critical process following cardiac ischemic injury. Here we determine that cyclin C, a component of the transcriptional regulator, Mediator complex, directly regulates cardiac and mitochondrial function by modifying mitochondrial fission. We tested the hypothesis that cyclin C has a binary function as a transcriptional cofactor in the nucleus and acute regulation of cardiac energetics in ischemia by enhancing mitochondrial fission in the cytoplasm.
In response to stress, cyclin C translocates to the cytoplasm enhancing mitochondria fission in part through interactions with Cdk1. Using cardiac specific cyclin C knockout and overexpression mouse models, we determined cyclin C regulates mitochondria morphology under basal and ischemic conditions in vivo. Furthermore, pretreatment with a Cdk1 inhibitor followed by ischemia in vivo results in reduced mitochondrial fission. Together, our study reveals that cyclin C regulates both hypertrophic gene expression and mitochondrial fission providing new insights into the regulation of cardiac energy metabolism following acute ischemic injury.
Cardiovascular genetics, Metabolism, Mitochondrial dynamics, Transcriptional regulation
xii, 137 pages
Includes bibliographical references (pages 129-137).
Copyright © 2019 Jessica Marie Ponce
Ponce, Jessica Marie. "Investigating the roles of cyclin C in the mammalian heart." PhD (Doctor of Philosophy) thesis, University of Iowa, 2019.