Environmental Sensitivity of Mitochondrial Gene Expression in Fish

Abstract

Maintaining energy organismal homeostasis under changing physiological and environmental conditions is vital, and requires constant adjustments of the energy metabolism. Central to meeting energy demands is the regulation of mitochondrial oxidative capacity. When demands increase, animals can increase mitochondrial content/enzymes, known as mitochondrial biogenesis. Central to mammalian mitochondrial biogenesis is the transcriptional master regulator PPARγ (peroxisome proliferator-activated receptor γ) coactivator-1α (PGC-1α), and the network of DNA-binding proteins it coactivates (e.g. nuclear respiratory factor 1 and 2 [NRF-1, NRF-2], estrogen-related receptor α [ERRα], thyroid receptor α [TRα-1], retinoid X receptor α [RXRα]). However, the mechanisms by which mitochondrial content in lower vertebrates such as fish is controlled are less studied. In my study I investigate underlying mechanisms of the phenomenon that many fish species alter mitochondrial enzyme activities, such as cytochrome c oxidase (COX) in response to low temperatures. In particular, I investigated (i) if the phenomenon of mitochondrial biogenesis during cold-acclimation is related to fish phylogeny, (ii) what role PGC-1α and other transcription factors play in mitochondrial biogenesis in fish, and (iii) if mRNA decay rates are important in the transcriptional control of a multimeric protein like COX. This study shows that mitochondrial biogenesis does not follow a phylogenetic pattern: while distantly related species displayed the same response to low temperatures, closely related species showed opposite responses. In species exhibiting mitochondrial biogenesis, little evidence was found for PGC-1α as a master regulator, whereas NRF-1 is supported to be an important regulator in mitochondrial biogenesis in fish. Further, there was little support for other transcription factors (NRF-2, ERRα, TRα-1, RXRα) to be part of the regulatory network. Lastly, results on the post-transcriptional control mechanism of mRNA decay indicate that this mechanism is important in the regulation of COX under mitochondrial biogenesis: it accounts for up to 30% of the change in subunit transcript levels. In summary, there is no simple temperature-dependent mitochondrial response ubiquitous in fish. Further, the pathways controlling mitochondrial content in fish differ from mammals in the important master regulator PGC-1α, however, NRF-1 is important in regulating cold-induced mitochondrial biogenesis in fish. Lastly, COX subunit mRNA decay rates seem to have a part in controlling COX amounts during mitochondrial biogenesis.