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Proteostasis is a challenge for cellular organisms, as all known protein synthesis machineries are error-prone. Here we show by cell fractionation and microscopy studies that misfolded proteins formed in the endoplasmic reticulum can become associated with and partly transported into mitochondria, resulting in impaired mitochondrial function. Blocking the endoplasmic reticulum-mitochondria encounter structure (ERMES), but not the mitochondrial sorting and assembly machinery (SAM) or the mitochondrial surveillance pathway components Msp1 and Vms1, abrogated mitochondrial sequestration of ER-misfolded proteins. We term this mitochondria-associated proteostatic mechanism for ER-misfolded proteins ERAMS (ER-associated mitochondrial sequestration). We testify to the relevance of this pathway by using mutant α-1-antitrypsin as an example of a human disease-related misfolded ER protein, and we hypothesize that ERAMS plays a role in pathological features such as mitochondrial dysfunction., Sanchón et al find that misfolded proteins formed in the ER can become associated with mitochondria, both in mammalian cells and in yeast, resulting in impaired mitochondrial function. They further discover that components of ERMES-mediated ER-mitochondria contacts are needed for this mechanism, which they name ERAMS, for ER-associated mitochondrial sequestration.

Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, in-vivo is associated with a subtle neurological phenotype. Brain mitochondria of homozygous knock-in mutant Mrps5V338Y/V338Y mice show decreased oxygen consumption and reduced ATP levels. Using a combination of unbiased RNA-Seq with untargeted metabolomics, we here demonstrate a concerted response, which alleviates the impaired functionality of OXPHOS complexes in Mrps5 mutant mice. This concerted response mitigates the age-associated decline in mitochondrial gene expression and compensates for impaired respiration by transcriptional upregulation of OXPHOS components together with anaplerotic replenishment of the TCA cycle (pyruvate, 2-ketoglutarate)., International Journal of Molecular Sciences, 22 (5), ISSN:1422-0067

The monohydration of SO2 has been achieved in solution mediated by a platinum-aquo complex. Benzamidate ligands play a key role along the process, acting as versatile proton shuttles. Finally, the platinum center allows the stabilization of benzimidic acid and a hydrogensulphite anion, the disfavored tautomers of benzamide and sulphonate, respectively., This work was supported by the Spanish MINECO/FEDER (Project CTQ2015-67461-P) and the Gobierno de Aragón and Fondo Social Europeo (Grupo de referencia E17_17R: Química Inorgánica y de los Compuestos Organometálicos).

The monohydration of SO2 has been achieved in solution mediated by a platinum-aquo complex. Benzamidate ligands play a key role along the process, acting as versatile proton shuttles. Finally, the platinum center allows the stabilization of benzimidic acid and a hydrogensulphite anion, the disfavored tautomers of benzamide and sulphonate, respectively.