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Yeasts are exposed to oxidative stress during routine metabolism, bioproduction, and interactions with other organisms. Here, the authors use a machine learning classifier to identify genes that are predictive of resistance to oxidative stress across diverse yeast species.

Here, the authors show that post-translational molecular signatures of human skeletal muscle in response to acute or chronic aerobic and resistance exercise are distinct, potentially dictating the differential physiologic adaptations to different exercise modes.

This study demonstrates that the MKK3b/6 signalling pathway drives the skeletal muscle growth-promoting effects of resistance exercise.

Mass spectrometry (MS) is a powerful tool for the structural characterization of protein complexes. Here the authors offer a path for direct integration of MS and electron microscopy with a MS approach that enables grid deposition and structural preservation of gaseous protein complex ions.

A mass spectrometry instrument control method—QuantMode—allows accurate, large-scale, multiplexed quantitative proteomics measurements using isobaric tagging by removing the problem of precursor interference. Also in this issue, Ting et al. provide a different solution to the same problem.

Inhibition of haem synthesis is shown to lead to the accumulation of branched-chain amino acids in the brown adipose tissue of mice, which reduces UCP1 levels and impairs thermogenesis.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

Systems genetics reveals interactions between host and microbial phenotypes in the murine gut, including a role for Akkermansia muciniphila in the production of immunomodulatory ornithine lipids.

The two major mechanisms for peptide fragmentation by mass spectrometry, collision-activated dissociation (CAD) or a newer method, electron transfer dissociation (ETD), display different efficacies for different peptide chemistries. A decision tree algorithm, which can be embedded into instruments with both CAD and ETD capabilities, selects the optimal fragmentation method to improve the chances of successful peptide identification.

The mitochondria houses several phosphatases, but their function is not well characterized. Here, the authors show that mitochondrial phosphatase Pptc7 is important during development for proper mitochondrial function and has a role regulating protein import with the translocase subunit Timm50.

Baker et al. show that mitochondrial stress recovery requires mobilization of lipid droplet triacylglycerol stores to facilitate cardiolipin biosynthesis and mitochondrial biogenesis.

Protein phosphorylation plays critical roles in myriad cell processes. In this work, the authors apply new mass spectrometer technology to detect and quantify tens of thousands of protein phosphorylation sites within one hour or less of analysis. This technology has potential to greatly accelerate biological discovery.

Deep proteome sequencing achieves ~80% coverage of the human proteome.

Coenzyme Q (CoQ) is a lipid made in the inner mitochondrial membrane with antioxidant roles throughout the cell, but regulation of its cellular distribution is unclear. Here the authors identify two proteins that have reciprocal CoQ trafficking functions to help coordinate CoQ localization in yeast.

Kodali, Proietti et al. report that increased numbers of P-bodies in leukaemia cells account for sequestration and prevention of tumour-suppressive mRNAs from being translated, which could be targeted as a potential intervention in myeloid leukaemia.

Bioactive small molecules mediate transcription factor functions to control cellular processes. Here, Liao et al. discover that a GATA1-regulated metabolic enzyme controls ceramide homeostasis to commission vital cytokine signaling for erythropoiesis.

The mitochondrial phosphatase PPTC7 has previously been linked to the maintenance of mitochondrial content, but the mechanisms underlying this phenotype remain unclear. Here, the authors demonstrate that loss of Pptc7 results in metabolic defects and further suggest that PPTC7 is a regulator of receptor-mediated mitophagy.

A method called neutron-encoding SILAC will enable higher-order multiplexing with high accuracy in quantitative proteomics experiments.

A method for the depolymerization of oxidized lignin under mild conditions in aqueous formic acid is described that results in more than 60 wt% yield of low-molecular-mass aromatics.

Tai et al. show that Hem25p—a mitochondrial glycine transporter required for haem biosynthesis—is also needed for isopentenyl pyrophosphate (IPP) transport into mitochondria and coenzyme Q synthesis in Saccharomyces cerevisiae.

A multiomics resource characterizing human mitochondrial proteins enables identification of biological functions and supports genetic diagnosis of mitochondrial pathologies.

Direct infusion–shotgun proteome analysis (DI-SPA) using data-independent acquisition mass spectrometry (DIA-MS) achieves fast and reproducible results by omitting the liquid-chromatography fractionation step and directly performing gas-phase peptide fractionation by ion mobility.

Mass spectrometry facilitates large-scale glycosylation profiling but in-depth analysis of intact glycopeptides is still challenging. Here, the authors show that activated ion electron transfer dissociation is suitable for glycopeptide fragmentation and improves glycoproteome coverage.

The Endoplasmic Reticulum acetylation machinery ensures proper quality control and disposal of newly folded proteins transiting the secretory pathway. Here, the authors show that this machinery acts as a metabolic regulator of acetyl-CoA homeostasis, impacting intracellular crosstalk.

Methods to assess organellar content are important. Here, Park et al develop a method for rapid isolation of early/sorting endosomes and demonstrate the application of the approach for analysis of endosomal proteomes and lipidomes, and for analysis of APP processing to Aβ via β and γ-Secretases.

A comparison of the proteomes and phosphoproteomes of four human embryonic stem cell lines and four induced pluripotent stem cell lines is reported, revealing subtle differences in these cell types at the protein level. Also introduced is the Stem Cell-Omics Repository (SCOR), a database of quantitative information for transcripts, proteins and post-translational modifications.

Proteomics, lipidomics and metabolomics of single gene deletion yeast strains sheds light on mitochondrial protein biology.

Linke et al. use unbiased and quantitative techniques to directly link both known and unknown liver and plasma lipid moieties to specific genomic loci, as compiled in a public web resource, LipidGenie. LipidGenie aided in the identification of a new group of sex-specific phosphatidylcholines.

Risk variants for ALS and FTD in the synaptic gene UNC13A increase the expression of an UNC13A cryptic exon in neurons with TDP-43 depletion.

Arginine methylation is an abundant post-translational modification catalysed by protein arginine methyltransferases (PRMTs). Here the authors use quantitative mass spectrometry to globally profile the substrates of the PRMT CARM1 in breast cancer cells, and establish a role for CARM1’s N-terminus in substrate recognition.

A chemical genetic approach to localize human Polo-like kinase 1 (Plk1) to distinct regions along the kinetochore–centromere axis combined with phosphoproteomic analysis reveals the presence of distinct Plk1 pools to mediate chromosomal segregation.

Thomas Drake and colleagues report the results of knockout or transgene introduction for nine obesity candidate genes in mice. Eight of the nine mutations result in significant changes in obesity-related traits, validating their previously developed approach for identifying candidate genes involved in particular phenotypes. They further identify related metabolic pathways that are altered by manipulation of the eight genes.

Thanks to advances in MS/MS acquisition rates and improvements in sample preparation and HPLC separation, it is now possible to analyze the yeast proteome in a single 70-min LC-MS/MS run.

A proteomic atlas of a model legume and its rhizobial symbiont provides a resource for understanding symbiotic nitrogen fixation.

The authors used liquid chromatography–mass spectrometry to compare the metabolic profile of non-fasted and fasted plasma samples in the Nile rat model of type 2 diabetes. Metabolite measurements in non-fasted samples were more reproducible than in fasted samples, supporting the use of non-fasted plasma metabolomics to study glucose tolerance in Nile rats during diabetes progression.

Directionality of the citrate/acetyl-CoA pathway transduce different signals is shown in mice overexpressing citrate transporters, SLC25A1 or SLC13A5.

Autism is a highly heritable neurodevelopmental disorder, and yet few specific susceptibility genes have been identified to date. A linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms is now described in a common set of 1,031 multiplex autism families. The linkage regions identified provide targets for rare variation screening whereas the discovery of a single novel association, SEMA5A, demonstrates the action of common variants.

This NeuCode SILAC/SILAM protocol uses neutron-coded lysine derivatives to improve stable isotope labeling of amino acids in cells or mice, enabling multiplexed comparison of proteomes from different samples by mass spectrometry–based proteomics.