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Mitochondrial mechanisms focus of study

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Posted October 2, 2018

Mysteries remain in your mitochondria, but researchers led by Rice University bioscientist Natasha Kirienko plan to bring them to light.

Kirienko is the first Rice faculty member to win a new class of grant from the National Institute of General Medical Sciences, one of the National Institutes of Health, called an R35. The five-year grant for nearly $2 million will support an effort by Kirienko and her team to refine their understanding of a pathway in mitochondria – the encapsulated “power plant” in every cell – that helps repair it when damaged.

Rice University bioscientist Natasha Kirienko has won a major National Institutes of Health grant to study protective biological pathways in mitochondria. Illustration by Jeff Fitlow

The grants are intended to maximize labs’ research time by alleviating the need to continually apply for NIH funding.

Kirienko’s work builds on her lab’s 2017 discovery of a previously unknown genetic pathway in mitochondria, one of three found so far that keep the organelle inside cells in good repair. Biological pathways pass signals from one protein to the next to activate metabolic processes.

Her paper in PLOS Genetics was the first to detail the mitochondrial function of the Ethanol and Stress Response Element (ESRE) pathway that appears to be triggered by the presence of ethanol.

“Most of us think of the mitochondria as the powerhouse of the cell, and indeed the generation of ATP is one of its most important functions,” said Kirienko, an assistant professor of biosciences whose lab uses worms as animal models to study biological pathways. “But in addition, they participate in multiple cell death signaling pathways, calcium flux, reactive oxygen species signaling and metabolite production and transport, so they are required for multiple processes that are absolutely essential for cellular homeostasis.”

Simply destroying damaged mitochondria is energetically costly, she said. “It’s always easier to repair something than to recycle,” Kirienko said.

That explains the presence of recently discovered mitochondrial surveillance pathways that work to keep them healthy. “When things become suboptimal, the pathways try to repair mitochondria before they are ultimately sent for degradation,” she said. Two such pathways were known before Kirienko’s discovery.

“The ESRE pathway is the one we know the least about,” she said. “A few other labs have found genes with ESRE elements in their promoter sequences on components related to hypoxia, response to ethanol or heat shock, but they were studying their given conditions, not the full pathway. That’s something we plan to do over the next two years, as well as to understand how these three mitochondrial pathways interact with each other.”

Knowing what activates the ESRE pathway will help treat disease, she said.

“Mitochondria are of particular interest because the largest pool of heritable genetic disease is related to mitochondrial disorders,” Kirienko said, noting Parkinson’s disease and muscle disorders have been linked to mitochondrial defects.

“About 6 percent of the nuclear genome encodes for proteins that function in mitochondria, and mitochondrial health is intimately linked to cellular and organismal health,” she said. “So being able to understand the pathways that monitor mitochondrial status and how we can activate them to keep mitochondria healthy could be of long-term benefit.”

Source: Rice University

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