bims-cytox1 2022-04-10 papers

Issue of 2022–04–10
three papers selected by
Gavin McStay, Staffordshire University

Cell Rep. 2022 Apr 05. pii: S2211-1247(22)00367-9. [Epub ahead of print]39(1): 110619

Coupling to Pam16 differentially controls the dual role of Pam18 in protein import and respiratory chain formation.

Chantal Priesnitz, Lena Böttinger, Nicole Zufall, Michael Gebert, Bernard Guiard, Martin van der Laan, Thomas Becker.

The presequence translocase (TIM23 complex) imports precursor proteins into the mitochondrial inner membrane and matrix. The presequence translocase-associated motor (PAM) provides a driving force for transport into the matrix. The J-protein Pam18 stimulates the ATPase activity of the mitochondrial Hsp70 (mtHsp70). Pam16 recruits Pam18 to the TIM23 complex to ensure protein import. The Pam16-Pam18 module also associates with components of the respiratory chain, but the function of the dual localization of Pam16-Pam18 is largely unknown. Here, we show that disruption of the Pam16-Pam18 heterodimer causes redistribution of Pam18 to the respiratory chain supercomplexes, where it forms a homodimer. Redistribution of Pam18 decreases protein import into mitochondria but stimulates mtHsp70-dependent assembly of respiratory chain complexes. We conclude that coupling to Pam16 differentially controls the dual function of Pam18. It recruits Pam18 to the TIM23 complex to promote protein import but attenuates the Pam18 function in the assembly of respiratory chain complexes.

Keywords: CP: Cell biology; CP: Metabolism; Pam18; TIM23 complex; cytochrome c oxidase; mitochondria; mtHsp70; protein sorting; respiratory chain

DOI: https://doi.org/10.1016/j.celrep.2022.110619

Mol Genet Genomic Med. 2022 Apr 07. e1943

Whole exome sequencing is an alternative method in the diagnosis of mitochondrial DNA diseases.

Chong Sun, Shengyang Wu, Ruiguo Chen, Junwu Liu, Jiasen Wang, Yanyun Ma, Zhulin Yuan, Yuezhen Li.

BACKGROUND: Mitochondrial disease (MD) is genetically a heterogeneous group of disorders with impairment in respiratory chain complexes or pathways associated with the mitochondrial function. Nowadays, it is still a challenge for the genetic screening of MD due to heteroplasmy of mitochondrial genome and the complex model of inheritance. This study was designed to investigate the feasibility of whole exome sequencing (WES)-based testing as an alternative option for the diagnosis of MD.
METHODS: A Chinese Han cohort of 48 patients with suspect MD features was tested using nanoWES, which was a self-designed WES technique that covered the complete mtDNA genome and 21,019 nuclear genes. Fourteen patients were identified with a single genetic variant and three with single deletion in mtDNA.
RESULTS: The heteroplasmy levels of variants in mitochondrial genome range from 11% to 100%. NanoWES failed to identify multiple deletions in mtDNA compared with long range PCR and massively parallel sequencing (LR-PCR/MPS). However, our testing showed obvious advantages in identifying variations in nuclear DNA. Based on nanoWES, we identified two patients with nuclear DNA variation. One of them showed Xp22.33-q28 duplication, which indicated a possibility of Klinefelter syndrome.
CONCLUSION: NanoWES yielded a diagnostic rate of 35.4% for MD. With the rapid advances of next generation sequencing technique and decrease in cost, we recommend the usage of nanoWES as a first-line method in clinical diagnosis.

Keywords: genetic diagnosis; mitochondrial disease; next generation sequencing; whole exome sequencing

DOI: https://doi.org/10.1002/mgg3.1943

Front Neurosci. 2022 ;16 818005

Photobiomodulation of Cytochrome c Oxidase by Chronic Transcranial Laser in Young and Aged Brains.

Fabrízio Dos Santos Cardoso, Douglas W Barrett, Zachary Wade, Sérgio Gomes da Silva, F Gonzalez-Lima.

In cellular bioenergetics, cytochrome c oxidase (CCO) is the enzyme responsible for oxygen consumption in the mitochondrial electron transport chain, which drives oxidative phosphorylation for adenosine triphosphate (ATP) production. CCO is also the major intracellular acceptor of photons in the light wavelengths used for photobiomodulation (PBM). Brain function is critically dependent on oxygen consumption by CCO for ATP production. Therefore, our objectives were (1) to conduct the first detailed brain mapping study of the effects of PBM on regional CCO activity, and (2) to compare the chronic effects of PBM on young and aged brains. Specifically, we used quantitative CCO histochemistry to map the differences in CCO activity of brain regions in healthy young (4 months old) and aged (20 months old) rats from control groups with sham stimulation and from treated groups with 58 consecutive days of transcranial laser PBM (810 nm wavelength and 100 mW power). We found that aging predominantly decreased regional brain CCO activity and systems-level functional connectivity, while the chronic laser stimulation predominantly reversed these age-related effects. We concluded that chronic PBM modified the effects of aging by causing the CCO activity on brain regions in laser-treated aged rats to reach levels similar to those found in young rats. Given the crucial role of CCO in bioenergetics, PBM may be used to augment brain and behavioral functions of older individuals by improving oxidative energy metabolism.

Keywords: aging; brain photobiomodulation; chronic laser therapy; controlled study; cytochrome oxidase histochemistry

DOI: https://doi.org/10.3389/fnins.2022.818005