Correction: Control of organelle gene expression by the mitochondrial transcription termination factor mTERF22 in Arabidopsis thaliana plants.

[This corrects the article DOI: 10.1371/journal.pone.0201631.].

Minerval (2-hydroxyoleic acid) causes cancer cell selective toxicity by uncoupling oxidative phosphorylation and compromising bioenergetic compensation capacity.

This work tests bioenergetic and cell-biological implications of the synthetic fatty acid Minerval (2-hydroxyoleic acid), previously demonstrated to act by activation of sphingomyelin synthase in the plasma membrane (PM) and lowering of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) and their carcinogenic signaling. We show here that Minerval also acts, selectively in cancer cell lines, as an ATP depleting uncoupler of mitochondrial oxidative phosphorylation (OxPhos). As a function of its exposure time, Minerval compromised the capacity of glioblastoma U87-MG cells to compensate for aberrant respiration by up-modulation of glycolysis. This effect was not exposure time-dependent in the lung carcinoma A549 cell line, which was more sensitive to Minerval. Compared with OxPhos inhibitors FCCP (uncoupler), rotenone (electron transfer inhibitor), and oligomycin (F1F0-ATPase inhibitor), Minerval action was similar only to that of FCCP. This similarity was manifested by mitochondrial membrane potential (MMP) depolarization, facilitation of oxygen consumption rate (OCR), restriction of mitochondrial and cellular reactive oxygen species (ROS) generation and mitochondrial fragmentation. Additionally, compared with other OxPhos inhibitors, Minerval uniquely induced ER stress in cancer cell lines. These new modes of action for Minerval, capitalizing on the high fatty acid requirements of cancer cells, can potentially enhance its cancer-selective toxicity and improve its therapeutic capacity.

Control of organelle gene expression by the mitochondrial transcription termination factor mTERF22 in Arabidopsis thaliana plants.

Mitochondria are key sites for cellular energy metabolism and are essential to cell survival. As descendants of eubacterial symbionts (specifically α-proteobacteria), mitochondria contain their own genomes (mtDNAs), RNAs and ribosomes. Plants need to coordinate their energy demands during particular growth and developmental stages. The regulation of mtDNA expression is critical for controlling the oxidative phosphorylation capacity in response to physiological or environmental signals. The mitochondrial transcription termination factor (mTERF) family has recently emerged as a central player in mitochondrial gene expression in various eukaryotes. Interestingly, the number of mTERFs has been greatly expanded in the nuclear genomes of plants, with more than 30 members in different angiosperms. The majority of the annotated mTERFs in plants are predicted to be plastid- or mitochondria-localized. These are therefore expected to play important roles in organellar gene expression in angiosperms. Yet, functions have been assigned to only a small fraction of these factors in plants. Here, we report the characterization of mTERF22 (At5g64950) which functions in the regulation of mtDNA transcription in Arabidopsis thaliana. GFP localization assays indicate that mTERF22 resides within the mitochondria. Disruption of mTERF22 function results in reduced mtRNA accumulation and altered organelle biogenesis. Transcriptomic and run-on experiments suggest that the phenotypes of mterf22 mutants are attributable, at least in part, to altered mitochondria transcription, and indicate that mTERF22 affects the expression of numerous mitochondrial genes in Arabidopsis plants.