bims-mitran 2022-07-24 papers

Issue of 2022–07–24
two papers selected by
Andreas Kohler, Stockholm University

Bio Protoc. 2022 May 20. 12(10): e4425

Purification of Mitochondrial Ribosomal Complexes from Trypanosoma cruzi and Leishmania tarentolae for Cryo-EM Analysis.

Stéphanie Durrieu-Gaillard, Marie Sissler, Yaser Hashem.

Kinetoplastids are unicellular eukaryotic parasites responsible for human pathologies such as Chagas disease, sleeping sickness or Leishmaniasis, caused by Trypanosoma cruzi, Trypanosoma brucei, and various Leishmania spp., respectively. They harbor a single large mitochondrion that is essential for the survival of the parasite. Interestingly, most of the mitochondrial gene expression machineries and processes present significant differences from their nuclear and cytosolic counterparts. A striking example concerns their mitochondrial ribosomes, in charge of translating the few essential mRNAs encoded by mitochondrial genomes. Here, we present a detailed protocol including the specific procedures to isolate mitochondria from two species of kinetoplastids, T. cruzi and L. tarentolae, by differential centrifugations. Then, we detail the protocol to purify mitochondrial ribosomal complexes from these two species of parasites (including ribosomal maturating complexes) by a sucrose gradient approach. Finally, we describe how to prepare cryo-electron microscopy (cryo-EM) grids from these two sorts of samples. This protocol will be useful for further studies aiming at analyzing mitochondrial translation regulation.

Keywords: Cryo-EM; Kinetoplastids mitochondria; Leishmania tarentolae; Mitoribosome; Mitoribosome biogenesis; Sucrose density gradient; Trypanosoma cruzi

DOI: https://doi.org/10.21769/BioProtoc.4425

Mol Oncol. 2022 Jul 17.

Mitochondrial DNA mutations in aging and cancer.

Anna Lm Smith, Julia C Whitehall, Laura C Greaves.

Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70. The pathologies of both aging and cancer have been characterized by respective groups of molecular hallmarks, and while some features are divergent between the two pathologies, several are shared. Perturbed mitochondrial function is one such common hallmark and this observation therefore suggests that mitochondrial alterations may be of significance in age-related cancer development. There is now considerable evidence documenting the accumulation of somatic mitochondrial DNA (mtDNA) mutations in aging human post-mitotic and replicative tissues. Similarly, mutations of the mitochondrial genome have been reported in human cancers for decades. The plethora of functions in which mitochondria partake, such as oxidative phosphorylation, redox balance, apoptosis, and numerous biosynthetic pathways, manifests a variety of ways in which alterations in mtDNA may contribute to tumor growth. However, the specific mechanisms by which mtDNA mutations contribute to tumor progression remain elusive and often contradictory. This review aims to consolidate current knowledge and describe future direction within the field.

Keywords: Aging; Cancer; Metabolism; Mitochondria; Mitochondrial DNA; Oxidative Phosphorylation

DOI: https://doi.org/10.1002/1878-0261.13291