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The work of four researchers at the University of South Alabama College of Medicine was recently published in the July 3 issue of Science Signaling.
Dr. Abu-Bakr Al-Mehdi, associate professor of pharmacology at the USA College of Medicine, along with Dr. Mark Gillespie, chair of pharmacology; Dr. Viktor Pastukh, pharmacology instructor; and Dr. Mikhail Alexeyev, associate professor of cell biology and neuroscience, co-authored the paper that outlines research conducted at USA.
“The results of our research contribute to the understanding of the pathophysiology of a variety of human diseases such as pulmonary hypertension, developmental abnormalities, cancer growth and other conditions where hypoxia is involved,” Dr. Al-Mehdi said.
Dr. Al-Mehdi said the information points to several new, interrelated concepts in hypoxic signaling. Hypoxia, or low blood oxygen, is a stimulus that serves as an inciting factor in cancerous tumor growth and other human diseases.
According to Dr. Al-Mehdi, the mitochondria – ultimate consumers of oxygen – are increasingly being recognized as a new player in cellular response to hypoxia.
“In this report, we show that mitochondria, the producers of energy and other signaling molecules, cluster around the nucleus for targeted delivery of oxidants to facilitate gene expression in cellular adaptation to hypoxia,” Dr. Al-Mehdi said. “This model of directed organellar migration is an exciting and novel paradigm in cellular signaling.”
Because the presence of hypoxia in solid tumors is an indicator of poor prognosis, Dr. Al-Mehdi said understanding the details of the transcriptional response to hypoxia may provide new targets for the therapeutic treatment of solid tumors.
“The major abnormalities in cancer are uncontrolled cellular proliferation and the ability of the cells to metastasize,” Dr. Al-Mehdi said. “Mitochondrial clustering may play a significant role in how cancer cells acquire the ability to colonize and proliferate in cancer tissues that are often low in oxygen.”
Dr. Al-Mehdi said the results from this study suggest that modulation of mitochondrial clustering may impact the progression and outcome of the disease processes involving hypoxia and point towards new drug development strategies that would target mitochondrial translocation.
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