bims-cytox1 2017-09-03 papers

Issue of 2017‒09‒03
three papers selected by
Gavin McStay
New York Institute of Technology

Sci Rep. 2017 Aug 25. 7(1): 9528

A missense MT-ND5 mutation in differentiated Parkinson Disease cytoplasmic hybrid induces ROS-dependent DNA Damage Response amplified by DROSHA.

Daniela Pignataro, Sofia Francia, Francesca Zanetta, Giulia Brenna, Stefania Brandini, Anna Olivieri, Antonio Torroni, Giuseppe Biamonti, Alessandra Montecucco.

Genome integrity is continuously threatened by endogenous sources of DNA damage including reactive oxygen species (ROS) produced by cell metabolism. Factors of the RNA interference (RNAi) machinery have been recently involved in the cellular response to DNA damage (DDR) in proliferating cells. To investigate the impact of component of RNAi machinery on DDR activation in terminally differentiated cells, we exploited cytoplasmic hybrid (cybrid) cell lines in which mitochondria of sporadic Parkinson's disease patients repopulate neuroblastoma SH-SY5Y-Rho(0) cells. Upon differentiation into dopaminergic neuron-like cells, PD63 cybrid showed increased intracellular level of ROS and chronic DDR activation, compared to other cybrids with the same nuclear background. Importantly, DDR activation in these cells can be prevented by ROS scavenging treatment suggesting that ROS production is indeed causative of nuclear DNA damage. Sequence analysis of the mitogenomes identified a rare and heteroplasmic missense mutation affecting a highly conserved residue of the ND5-subunit of respiratory complex I, which accounts for ROS increase. We demonstrated that the assembly of nuclear DDR foci elicited by oxidative stress in these cells relies on DROSHA, providing the first evidence that components of RNAi machinery play a crucial role also in the mounting of ROS-induced DDR in non-replicating neuronal cells.

DOI: https://doi.org/10.1038/s41598-017-09910-x

Biochimie. 2017 Aug 23. pii: S0300-9084(17)30222-5. [Epub ahead of print]

Role of cardiolipin in stability of integral membrane proteins.

Andrej Musatov, Erik Sedlák.

Cardiolipin (CL) is a unique phospholipid with a dimeric structure having four acyl chains and two phosphate groups found almost exclusively in certain membranes of bacteria and of mitochondria of eukaryotes. CL interacts with numerous proteins and has been implicated in function and stabilization of several integral membrane proteins (IMPs). While both functional and stabilization roles of CL in IMPs has been generally acknowledged, there are, in fact, only limited number of quantitative analysis that support this function of CL. This is likely caused by relatively complex determination of parameters characterizing stability of IMPs and particularly intricate assessment of role of specific PLs such as CL in IMPs stability. This review aims to summarize quantitative findings regarding stabilization role of CL in IMPs reported up to now.

Keywords: Delipidation; Kinetic stability; Membrane protein stability; Protein-lipid interaction

DOI: https://doi.org/10.1016/j.biochi.2017.08.013

Mitochondrion. 2017 Aug 22. pii: S1567-7249(17)30234-9. [Epub ahead of print]

Mitochondria and the eye disease.

M Kolko.

DOI: https://doi.org/10.1016/j.mito.2017.08.010