Grauvogel, L. | bioRxiv Science

bioRxiv2026

Scanning DIA on the ZenoTOF 8600 system enables ultra-sensitive and quantitative proteomics from single cells to post-translational modifications in a compact platform

Mass spectrometry-based proteomics increasingly demands platforms that combine quantitative rigor with the discovery capabilities of accurate mass systems. Here we present the ZenoTOF 8600 system, a compact mass spectrometry system that integrates enhanced ion capture and transmission optics with an optical detection system, Zeno trap-enhanced MS/MS, electron-activated dissociation, and scanning quadrupole data-independent acquisition (ZT Scan DIA). We show that ZT Scan DIA outperforms conventional variable-window DIA (Zeno SWATH DIA) in both identifications and quantitative reproducibility, and demonstrate the platforms versatility across proteomics applications: thousands of protein groups from bulk samples at up to 500 samples per day, single-cell proteomics yielding up to 4,700 proteins, accurate ratio recovery in mixed-species quantitative benchmarks, low-attomole targeted quantitation, and detection of disease-relevant phosphorylation in a Parkinsons disease cellular model using complementary CID and EAD fragmentation. The instruments compact footprint makes it attractive for settings where both analytical breadth and operational robustness are required.

biophysics↗

bioRxiv2024

Cardiomyocyte PGC-1α enables physiological adaptations to endurance exercise through suppression of GDF15 and cardiac atrophy

Exercise training induces physiological cardiac hypertrophy, enhanced mitochondrial biogenesis and myocardial contractility. In skeletal muscle, the transcriptional coactivator PGC-1 is a key orchestrator of these responses. The heart expresses abundant and exercise-responsive PGC-1, but it is unclear whether cardiomyocyte PGC-1 is necessary for cardiac adaptation to endurance training. Here we demonstrate that cardiomyocyte PGC-1 is required for physiological cardiac hypertrophy during exercise training in mice. In the absence of cardiomyocyte PGC-1, voluntary wheel running does not improve exercise capacity and instead confers immune-fibrotic-atrophic heart failure after just 6 weeks of training. We identify cardiomyocyte PGC-1 as a negative regulator of stress-responsive senescence gene expression. The most enriched of these is the myomitokine GDF15. GDF15 is secreted locally but not systemically in PGC-1-deficient mouse hearts and reduces cardiomyocyte size. Cardiomyocyte-specific reduction of GDF15 expression preserves exercise tolerance and cardiac contractility in PGC-1-deficient mice during endurance training. Finally, we show that cardiomyocyte PPARGC1A expression correlates with cardiomyocyte number and negatively with GDF15 expression in human cardiomyopathies through single nucleus RNA sequencing. Our data implicate cardiomyocyte PGC-1 as a vital safeguard against stress-induced atrophy and local GDF15-induced dysfunction during exercise.

physiology↗