Hashimi 2013 Abstract MiP2013
Hashimi H, McDonald L, StΕΓbrnΓ‘ E, LukeΕ‘ J(2013) Ancestral function of Letm1 as determined in the evolutionary diverged pathogen Trypanosoma brucei. Mitochondr Physiol Network 18.08. |
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MiP2013, Book of Abstracts Open Access
Hashimi H, McDonald L, Stribrna E, Lukes J (2013)
Event: MiPNet18.08_MiP2013
Leucine zipper EF-hand containing transmembrane protein 1 (Letm1) is evolutionarily conserved in diverse eukaryotic lineages having energized mitochondria, from opisthokonts, comprising metazoa and fungi, to plastid containing plants and apicomplexans. Its deletion from the human genome has been implicated in causing the seizure symptoms of Wolf-Hirschhorn syndrome. Research in predominantly opsithokont model systems has resulted in disparate roles of Letm1 such as a cation/proton antiporter, translocating either potassium or calcium across the inner membrane (mtIM), and anchoring of mitochondrial ribosomes to facilitate mtIM incorporation of hydrophobic respiratory system subunits.
We have undertaken functional analysis of Letm1 in the highly evolutionarily diverged Trypanosoma brucei, member of the excavate order Kinetoplastida, taking advantage of the existence of in vitro cultured forms bearing mitochondria with different physiological states, including a petite mutant-like organelle. RNAi-interference in all of these cell types results in swelling that can be mitigated by the ionophore nigericin, suggesting that it plays a role in the efflux of the cation from the matrix. An observed effect on mitochondrial translation is a downstream effect of potassium accumulation in the organelle.
By comparison of our results with those from other systems, we conclude that the basal function of Letm1 is to regulate potassium efflux from the matrix to maintain mitochondrial volume. The protein shows remarkable conservation of function not only across wide evolutionary distances, but also in different mitochondrial states. T. brucei is an appealing model for study of mitochondrial biology due to its amenability to reverse genetics, existence of in vitro cultures bearing different mitochondria and its diverged position in the eukaryotic tree of life, bringing another perspective for comparative biochemical approaches.
Labels: MiParea: mt-Structure;fission;fusion, nDNA;cell genetics, Comparative MiP;environmental MiP
Organism: Protists
Regulation: Ion;substrate transport
MiP2013, Trypanosoma brucei, S06
Affiliations and author contributions
Institute of Parasitology, Biology Centre, Czech Academy of Sciences and Faculty of Science, University of South Bohemia, Czech Republic. - Email: [email protected]