bims-cytox1 2022-01-09 papers

Issue of 2022–01–09
three papers selected by
Gavin McStay, Staffordshire University

STAR Protoc. 2021 Dec 17. 2(4): 101021

Analyzing the integrity of oxidative phosphorylation complexes in Drosophila flight muscles.

Drosophila flight muscles are highly enriched with mitochondria and have emerged as a powerful genetic system for studying how oxidative phosphorylation (OXPHOS) complexes are assembled. Here, we describe a series of protocols for analyzing the integrity of OXPHOS complexes in Drosophila via blue native polyacrylamide gel electrophoresis (BN PAGE). We have also included protocols for the additional steps that are typically performed after OXPHOS complexes are separated by BN PAGE, such as Coomassie staining, silver staining, and in-gel OXPHOS activities. For complete details on the use and execution of this protocol, please refer to Murari et al. (2020).

Keywords: Cell Biology; Genetics; Metabolism; Model Organisms; Protein Biochemistry

DOI: https://doi.org/10.1016/j.xpro.2021.101021

BMC Biol. 2022 Jan 07. 20(1): 12

mtIF3 is locally translated in axons and regulates mitochondrial translation for axonal growth.

Soyeon Lee, Dongkeun Park, Chunghun Lim, Jae-Ick Kim, Kyung-Tai Min.

BACKGROUND: The establishment and maintenance of functional neural connections relies on appropriate distribution and localization of mitochondria in neurites, as these organelles provide essential energy and metabolites. In particular, mitochondria are transported to axons and support local energy production to maintain energy-demanding neuronal processes including axon branching, growth, and regeneration. Additionally, local protein synthesis is required for structural and functional changes in axons, with nuclear-encoded mitochondrial mRNAs having been found localized in axons. However, it remains unclear whether these mRNAs are locally translated and whether the potential translated mitochondrial proteins are involved in the regulation of mitochondrial functions in axons. Here, we aim to further understand the purpose of such compartmentalization by focusing on the role of mitochondrial initiation factor 3 (mtIF3), whose nuclear-encoded transcripts have been shown to be present in axonal growth cones.
RESULTS: We demonstrate that brain-derived neurotrophic factor (BDNF) induces local translation of mtIF3 mRNA in axonal growth cones. Subsequently, mtIF3 protein is translocated into axonal mitochondria and promotes mitochondrial translation as assessed by our newly developed bimolecular fluorescence complementation sensor for the assembly of mitochondrial ribosomes. We further show that BDNF-induced axonal growth requires mtIF3-dependent mitochondrial translation in distal axons.
CONCLUSION: We describe a previously unknown function of mitochondrial initiation factor 3 (mtIF3) in axonal protein synthesis and development. These findings provide insight into the way neurons adaptively control mitochondrial physiology and axonal development via local mtIF3 translation.

Keywords: Axon development; Bimolecular fluorescence complementation; Local translation; Mitochondria; Mitochondrial translation

DOI: https://doi.org/10.1186/s12915-021-01215-w

Clin Chim Acta. 2022 Jan 03. pii: S0009-8981(21)00454-X. [Epub ahead of print]

Clinical and genetic analysis of combined oxidative phosphorylation defificiency-10 caused by MTO1 mutation.

Chaofan Zhou, Jin Wang, Qinle Zhang, Qi Yang, Shang Yi, Yiping Shen, Jingsi Luo, Zailong Qin.

The mitochondrial translation optimization factor 1(MTO1) gene mutations had been reported to be linked to combined oxidative phosphorylation defificiency-10 (COXPD10). In this study, we presented the detailed clinical features and genetic analysis of the patient with two variants in MTO1, and reviewed 42 different cases available in publications. Whole exome sequencing and bioinformatics analysis were employed to detect the genetic variants of a 6-month-old boy with metabolic disorder and multiple organ failure; Sanger sequencing was performed to confirm the origin of variants; and clinical data of the patients was retrospectively collected and analyzed. Variant classification was followed to ACMG guidline. The proband was diagnosed with multiple organ failure, severe pneumonia, sepsis, hyperlactatemia, metabolic acidosis, and moderate anemia. Compound heterozygous mutations in the coding region of MTO1 gene (c.1291C>T/p.Arg431Trp and c.1390C>T/p.Arg464Cys) were identified, and the results of family verification experiment showed that the mutations were inherited from the parents, respectively. Combined with clinical symptoms, the patient was diagnosed as COXPD10. In summary, hallmark features of MTO1 mutations were lactic acidosis and hypertrophic cardiomyopathy. Of note, patients with the same genetic mutation may not have the same clinical presentation. Additional MTO1 defificiency cases will help to make genotype-phenotype correlations clearer.

Keywords: COXPD10; Genotype-phenotype, Whole exome sequencing; MTO1; Mitochondrial diseases

DOI: https://doi.org/10.1016/j.cca.2021.12.025