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International Foundation for Optic Nerve Disease

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Mitochondrial Regulation

Unravelling the complexity of mitochondrial function and regulation is fundamental to understanding health and disease. This is very relevant to major disease groups such as cancer, vascular disease, dementia, and other nervous system disorders including optic nerve disease.

It is important to understand not only genetics of the DNA of the cell nucleus and mitochondria, but also the mechanisms of transcription of the genes of the DNA to the RNA intermediaries; the role of non coding RNA; post transcriptional changes on RNA; the translation of the RNA to functioning proteins, as well as post translational changes to those proteins and influences on protein functions. Recent experimental work is uncovering this regulatory complexity and opening opportunities for therapies. Much more work is needed.

The Medical Research Council, one of seven tax payer funded Research Councils in Great Britain, has an annual expenditure of about £ 3/4 billion. It has recently sponsored an open access review of advances in Regulation of Mammalian Mitochondrial Gene Expression done by authors in the MRC's Mitochondrial Biology Unit in Cambridge.

Other References:

The mitochondrial epitranscriptome: the roles of RNA modifications in mitochondrial translation and human disease Bohnsack, M.T. & Sloan, K.E. Cell. Mol. Life Sci. (2017).

Regulation of neuronal gene expression by local axonal translation Lulu I T. Korsak, Ph.D., Molly E. Mitchell, Katherine A. Shepard, M.S., and Michael R. Akins, Ph.D. Curr Genet Med Rep. 2016 Mar;4(1):16-25. Epub 2016 Feb 6.

Long noncoding RNAs coordinate functions between mitochondria and the nucleus. Yaru Dong, Takeshi Yoshitomi, Ji-Fan Hu and Jizhe Cui. Epigenetics & Chromatin 201710:41. This work was supported by grants from the Natural Science Foundation of China (81100695, 31430021); the National Basic Research Program of China (2015CB943303); and the Basic Science Foundation of Jilin University (201103049).

Proteostasis, oxidative stress and aging. Ioanna Korovila, Martín Hugo, José Pedro Castro, Daniela Weber, Annika Höhn, Tilman Grune and Tobias Junga. Redox Biol. 2017 Oct; 13: 550–567. Published online 2017 Jul 12. doi: 10.1016/j.redox.2017.07.008

Regulation of Mitochondrial Respiratory Chain Biogenesis by Estrogens/Estrogen Receptors and Physiological, Pathological and Pharmacological Implications Jin-Qiang Chen, Patrick R. Cammarata, Christopher P. Baines, and James D. Yager. Biochim Biophys Acta. 2009 Oct; 1793(10): 1540–1570. Published online 2009 Jun 23. doi: 10.1016/j.bbamcr.2009.06.001

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