by Pavithr Goli
Famously known as the “Powerhouse of the Cell”, the mitochondria is vital as it provides the human body with the necessary energy to function on a day-to-day basis. In addition to this main role, researchers have recently discovered other mitochondrial functions critical to human survival such as interacting with pathogens during infections and metabolizing cholesterol (1). These often overlooked features of mitochondrial function have intrigued Dr. Natasha Kirienko, an Associate Professor in the Department of Biosciences at Rice, who has been studying mitochondrial surveillance pathways and damaged mitochondria. Furthermore, Dr. Kirienko has spent time studying how both can be utilized in anticancer therapeutics, which can potentially change the approach taken to treat cancer, saving numerous lives in the process.
Dr. Kirienko joined Rice University in 2015 after she earned a $2 million grant from CPRIT (Cancer Prevention & Research Institute of Texas). After earning her undergraduate and graduate degrees in biochemistry and biology in Russia, Dr. Kirienko came to the United States to work on her Ph.D. After receiving her Ph.D. in molecular biology from the University of Wyoming, Dr. Kirienko worked as a postdoctoral research fellow at the Massachusetts General Hospital and Harvard Medical School before joining Rice to continue her groundbreaking research on mitochondria. Dr. Kirienko developed her fascination for mitochondria during her time in graduate school where she was interested in why “mitochondria had lower efficiency in leukemia” and why “they had a poor ability to convert electrons into ATP.”
As someone who has “always [been] interested in identifying fundamental principles of why things are working,” Dr. Kirienko was curious about the effect of disease on mitochondria and, “the biochemical basis of the cancer cells /cell lines.” This interest in studying the pathogenesis of mitochondria propelled her to begin conducting research and investigating the response of damaged mitochondria and the strategies these damaged structures employ to recover when pathogens impact their function.
Dr. Kirienko spent years dedicated to developing a greater understanding of mitochondria with the hope that a new therapeutic method to fight cancer could be developed. This interest in understanding fundamental principles led Dr. Kirienko to focus her research on one of the most fundamental and basic organisms that exist: Caenorhabditis elegans or C. elegans (2). A roundworm commonly used in scientific research as a model organism, C. elegans has been instrumental in understanding the various molecular and genetic mechanisms the human body employs when responding to diseases like cancer (2).
Using this model organism and previous literature as a guide, Dr. Kirienko has been able to observe novel pathways in mitochondria and find drugs that induce mitochondrial damage, pushing “cancer cells [to] undergo cell death like paraptosis or apoptosis.” The goal of Dr. Kirienko’s current approach is to apply this novel method of inducing cell death on ''different cancer cell types” or combine it with current anticancer drugs in a synergistic manner to create highly selective treatments capable of killing cancer cells and sparing healthy ones. This approach will help reduce the side effects commonly seen in cancer treatment while maintaining the treatment’s effectiveness.
To further her research, Dr. Kirienko uses an interdisciplinary approach by working with physical chemists and doctors to help ensure that her novel cancer therapy will be applicable beyond C. elegans. She hopes that physical chemists can optimize the drugs that Dr. Kirienko found by “synthesizing and improving the physical structure of the drug.” After further testing on mice and cell cultures, Dr. Kirienko intends to expand her research and consult the help of physicians in a potential clinical study.
Along with her cancer research, Dr. Kirienko has expanded her lab’s focus on other diseases caused by poor mitochondrial health such as Alzheimer’s disease. Specifically, she and her lab are trying to understand whether improving mitochondrial health may be beneficial for neuronal function. In order to understand this mechanism further Dr. Kirienko is attempting to use various biomolecules to avoid cellular death by activating mitochondria and “[finding] a way to help mitochondria fix themselves quicker.”
Furthermore, Dr. Kirienko and her lab are attempting to observe mitochondrial reactions to infections. Using C. elegans as their model organisms, they are interested in “looking at basic toxins that damage mitochondria.” One specific group of toxins that they are investigating are siderophores, which are “small molecules with a peptide side chain… [that] are secreted in the body and release iron.” During a bacterial infection, the bacterial pathogen uses its siderophore to absorb iron from the host, enabling the bacteria to grow and infect the cells. The mitochondria are the site of electron transport chains (ETCs), which contain several iron-rich proteins that help generate energy for the cell; unfortunately, when “iron is stolen, the mitochondria get damaged.” (3).To better study this mysterious process, Dr. Kirienko and her lab have “developed a cell culture model where [they] can assess the pathogenicity of bacteria.” They aim to use this newly developed model to elucidate the reactions and mechanisms that allow pathogenic bacteria to hijack cellular mechanisms.
Beyond discovering mitochondrial pathways and reactions to infections, Dr. Kirienko's lab is eager to explore "mitophagy or mitochondrial turnover, applied to cancer… [and] study more mitochondrial pathways.” She hypothesizes that this research can provide key information in finding ways to strengthen mitochondrial health so that mitochondrial cells can effectively withstand deadly pathogens and diseases, ultimately leading to longevity in human health.
Dr. Kirienko and her lab have been working on some groundbreaking research for the past five years. Using novel methods and ingenuity, Dr. Kirienko has already made major strides in the field of cancer therapy and molecular biology. Through her current projects and the future endeavors that she hopes her lab can make, Dr. Kirienko intends to understand more about the powerhouse of the cell and use it to develop influential cancer therapies.
Works Cited:
(1)Wallace, Douglas C. “Mitochondria and cancer.” Nature reviews. Cancer vol. 12,10 (2012): 685-98. doi:10.1038/nrc3365
(2)Why Study C. Elegans?, Dr. Lundquist, 01/19/21, www.people.ku.edu/~erikl/Lundquist_Lab/Why_study_C._elegans.html
(3) Montine TJ, Morrow JD. Fatty acid oxidation in the pathogenesis of Alzheimer's disease. Am J Pathol. 2005 May;166(5):1283-9. doi: 10.1016/S0002-9440(10)62347-4. PMID: 15855630; PMCID: PMC1606384.