Shiori Sekine, PhD
Assistant Professor of Medicine
Division of Cardiology
Our lab is interested in the molecular mechanisms regulating mitochondrial stress responses.
Shiori Sekine Lab
Mitochondria are considered to have evolved from bacteria that invaded our ancestral cells about 300 million years ago (endosymbiotic theory). However, mitochondria are now intricately involved in various function within the cells, and their existence has become indispensable for our vital activities.
During the process of performing their variety of functions, mitochondria are constantly exposed to various stresses. For example, ROS, inevitable byproducts of the ATP production, damage mitochondria by oxidizing mitochondrial membrane lipids and proteins. Recent research has revealed that mitochondria are equipped with several strategies to cope with these stresses and maintain the quality of mitochondria. These mechanisms are called the “mitochondrial stress response” or “mitochondrial quality control”. For example, mitophagy is a mechanism that eliminates dysfunctional mitochondria from the cells by autophagy. It has been found that mitochondria are actively communicating with other intracellular organelles to evoke the proper stress response. For example, the accumulation of abnormal mitochondrial proteins has been shown to be signaled to the nucleus and promote a specific transcriptional program to relieve mitochondrial proteotoxic stress (mtUPR). In order to drive these mitochondrial stress responses, proteins that can monitor the abnormalities in mitochondria and transmit that information to other proteins are necessary. In our laboratory, we are interested in identifying critical molecular players in mitochondrial stress responses and elucidating their roles. Our mission is therefore to enhance human health through basic mitochondrial biology research.
What question I’d like to answer
Can you improve human health by modulating the mitochondrial stress response?
For more information: https://www.shiorilab.net
Shiori received her PhD degree in Pharmaceutical Sciences from the University of Tokyo, Japan in 2011. She led a small research group as an Assistant Professor in Dr. Hidenori Ichijo’s lab at the University of Tokyo from 2011 to 2016. During this time, she worked on the analysis of mitochondrial protein phosphatase PGAM5, and uncovered its role in metabolic stress responses. In 2016, she was selected as a Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellow for Research Abroad, and joined Dr. Richard J. Youle’s lab in NIH, NINDS. In Dr. Youle’s lab, she elucidated the mitochondrial stress-dependent activation mechanisms of mitochondrial protein kinase PINK1. In 2019, she was appointed as an Assistant Professor in the Aging Institute at the University of Pittsburgh, and started her own independent lab.
Read more: Department of Medicine Faculty Profile
Houston R, Sekine Y, Larsen MB, Murakami K, Mullett SJ, Wendell SG, Narendra DP, Chen BB, Sekine S*. Discovery of bactericides as an acute mitochondrial membrane damage inducer. Mol Biol Cell. 2021 Sep 8:mbcE21040191. doi: 10.1091/mbc.E21-04-0191. Epub ahead of print. PMID: 34495738. *Corresponding author
Sekine S, Wang C, Sideris DP, Bunker E, Zhang Z, Youle RJ. Reciprocal Roles of Tom7 and OMA1 during Mitochondrial Import and Activation of PINK1. Mol Cell. 2019 Mar 7;73(5):1028-1043.e5. doi: 10.1016/j.molcel.2019.01.002. Epub 2019 Feb 4. PMID: 30733118.
Sekine S, Youle RJ. PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol. BMC Biol. 2018 Jan 10;16(1):2. doi: 10.1186/s12915-017-0470-7. PMID: 29325568; PMCID: PMC5795276.
Sekine S*, Yao A*, Hattori K, Sugawara S, Naguro I, Koike M, Uchiyama Y, Takeda K, Ichijo H. The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress. EBioMedicine. 2016 Jan 29;5:82-92. doi: 10.1016/j.ebiom.2016.01.031. PMID: 27077115; PMCID: PMC4816851. *co-first author
Sekine S, Kanamaru Y, Koike M, Nishihara A, Okada M, Kinoshita H, Kamiyama M, Maruyama J, Uchiyama Y, Ishihara N, Takeda K, Ichijo H. Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5. J Biol Chem. 2012 Oct 5;287(41):34635-45. doi: 10.1074/jbc.M112.357509. Epub 2012 Aug 22. PMID: 22915595; PMCID: PMC3464569.
Current Lab Members
Ryan Houston, Research Technician