I am a Berlin-bred scientist, who has carried out research around the globe from Berlin, Edinburgh (UK), Ithaca (USA), Perth (Australia) to Helsinki (Finland). As a child from behind the Iron Curtain, I dreamt myself to the stars by watching Blade Runner, Star Wars, and Star Trek. In hindsight, no wonder I started to study biology and specifically midi-chlorians, I mean mitochondria, of course. Mitochondria are the energy-generating organelles of our cells, or as Jedi master Qui-Gon put it “…are microscopic life-forms that reside within the cells of all living things and communicate with the force.” In my research I have identified a gene expression quality control process that is fighting bad protein production inside mitochondria. In future work, I would like to capitalize on this finding and determine the key factors involved in this quality control process. Secondly, I will study how the rest of the cell responds to bad protein production in mitochondria. We suspect such understanding is key to the development of pharmacological treatments for mitochondrial disease caused by gene expression defects; patients who suffer from these disorders have no treatment option to date. To once more quote Qui-Gon: “When you learn to quiet your mind, you will hear them speaking to you.” As a Newcastle University Academic Track (NUAcT) fellow here in Newcastle at the Wellcome Centre for Mitochondrial Research, I will endeavor to understand how stressed mitochondria speak to us, aiming to improve the life of patients with mitochondrial disease. May the force be with us!
Dissecting a novel quality control pathway in mitochondria.
Principal Investigators: Dr Uwe Richter
Other staff members involved: PhD(c) Omid Safronov and Dr. Ana Andjelkovic
Mitochondrial diseases are often caused by mutations in enzymes required for the expression of the second genome in our cells, the mitochondrial DNA. The genes encoded in the mtDNA are strictly required for O2 coupled energy production. But mitochondrial gene expression disorders are characterised by a very heterogeneous clinical presentation that cannot be explained by simple loss of energy production. Instead, it suggests that dependent on the specific defect in mitochondrial gene expression, very different molecular aberrations and cellular consequences occur. The lack of understanding of these molecular mechanisms is clearly one reason for that there are still no curative treatments for this group of disorders. The two specific goals of our research are to 1) better our understanding of the primary molecular aberrations in mitochondrial gene expression disease by investigating dedicated quality control mechanisms and 2) to identify the signalling network(s) that communicate distinct aberrations in mitochondrial gene expression to the nucleo-cytoplasmic gene expression machinery. Such knowledge will be instrumental to find novel targets for improved diagnostics and pharmacological treatments for patients with no treatment option to date.
Sponsor/Funder: NUAcT fellow program, Newcastle University; Academy of Finland Research fellow grant.
Richter U, Lahtinen T, Marttinen P, Myöhänen M, Greco G, Cannino G, Jacobs HT, Lietzén N, Nyman TA and Battersby BJ (2013). A mitochondrial ribosomal and RNA decay pathway blocks cell proliferation. Current Biology 23, 535–541.
Richter U, Lahtinen T, Marttinen P, Suomi F and Battersby BJ (2015). Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness. Journal of Cell Biology, 211(2), 373-389.
Richter U, Evans M, Clark W, Marttinen P, Shoubridge EA, Suomalainen A, Wredenberg A, Wedell A, Pan T, and Battersby BJ (2018). RNA modification landscape of the human mitochondrial tRNALys regulates protein synthesis. Nature Communications.
Richter U, Ng KY, Suomi F, Marttinen P, Turunen T, Jackson C, Suomalainen A, Vihinen H, Jokitalo E, Nyman TA, Isokallio M, Stewart JB, Mancini C, Brusco A, Seneca S, Lombès A, Taylor RW, and Battersby BJ (2019). A mitochondrial stress response triggered by defects in protein synthesis quality control, Life Science Alliance.