Publication Date

2019-12-12

Availability

Embargoed

Embargo Period

2021-12-11

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Marine Biology and Ecology (Marine)

Date of Defense

2019-10-29

First Committee Member

Michael C. Schmale

Second Committee Member

Margie F. Oleksiak

Third Committee Member

M. Danielle McDonald

Fourth Committee Member

Antonio Barrientos

Fifth Committee Member

Enrique Mesri

Abstract

Damselfish neurofibromatosis (DNF) is a type of cancer affecting Stegastes partitus (Bicolor damselfish) on Florida reefs. The agent which causes the disease, termed the damselfish virus-like agent (DVLA), is the only known agent to replicate within mitochondria of animal cells. Determining the effects DVLA has on mitochondrial function and DNA levels are of importance to further understand DNF, as well as which mechanisms of mitochondrial function are directly affected by DVLA which may cause cancer. Experiments analyzed DNA levels of both DVLA and mitochondria (mtDNA), as well as mitochondrial-mediated metabolism on healthy and tumor tissues. Cell lines were also analyzed for DNA levels and metabolism, as well as mitochondrial mass and mitochondrial membrane potential. DNA results for both tissues and cell lines suggested DVLA DNA competes with mtDNA for replicative factors and decreases mtDNA replication through some unknown mechanism. Metabolic results of nodular tumors suggested mitochondrial-mediated metabolism is significantly decreased for several respiratory states/complexes in comparison to healthy skin, while cell lines metabolic results were inconclusive due to the cellular environment created by the supplemented growth media used in vitro. Overall, the presence of DVLA within tissues may initiate a cascade of events that initially decreases mtDNA replication, leading to decreases in mtRNA synthesis, which may trigger a cascade of events that upregulates/downregulates cell signaling pathways. Changes related to cell signaling pathways may include deregulated metabolism, sustaining proliferative signaling and resisting cell death, which are all hallmarks of cancer.

Keywords

Mitochondria; Cancer; Damselfish; Neurofibromatosis; Virus; Metabolism

Available for download on Saturday, December 11, 2021

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