Biology subjects

Heim, B.

Publications and source records attributed to Heim, B..

3 recordsLinked to original sources

bioRxiv2023

Investigation of Volatile Metabolites in Sebum as Prodromal Indicators of Parkinson's Disease

Parkinsons Disease (PD) has been associated with a distinct odour, which emanates from the skin and is strongest in sebum-rich areas. In this study, sebum was sampled from participants using cotton gauze and the volatile components emanating from these swabs were analysed directly with thermal desorption gas chromatography - mass spectrometry (TD GC-MS). We analysed subjects with clinically established PD (n=46) along with healthy controls (n=28) sampled from two sites. The volatilome profiles obtained for PD and control cohorts were compared with the profile of participants (n=9) with isolated REM sleep behaviour disorder (iRBD) to investigate metabolite changes in probable prodromal PD. We also compared PD participants sampled at yearly intervals for a total of three years. Volatile compounds from TD GC-MS analysis were found in different quantities between PD, control and iRBD subjects. We found 55 significant features where abundance in samples from individuals with iRBD was intermediate between that found for PD and control samples. Significant features were found to be alkanes and fatty acid methyl esters (FAMEs), with other metabolites identified as an aldehyde, purine and tropinone. In olfactory analysis of the iRBD samples three out of nine were classified PD, and on clinical follow up two of these showed PD symptoms. Further, when analysing the volatilome from longitudinal PD sampling, almost two-thirds of the significant features showed differential regulation over the three visits. Our findings support the use of sebum as an accessible biofluid rich with measurable volatile compounds which alter in abundance in individuals with PD and iRBD, as the disease progresses.

neuroscience↗

bioRxiv2023

Molecular control of endurance training adaptation in mouse skeletal muscle

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. While morphological changes in endurance-trained muscles are well-described, the molecular underpinnings of training adaptation are poorly understood. We aimed at defining the molecular signature of a trained muscle and unraveling the training statusdependent responses to an acute bout of exercise. Our results reveal that even though at baseline, the transcriptomes of trained and untrained muscles are very similar, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively, in part mediated by epigenetic modifications. Second, proteomic changes were elicited by different transcriptional modalities. Finally, transiently activated factors such as the peroxisome proliferator-activated receptor {gamma} coactivator 1 (PGC-1) are indispensable for normal training adaptation. Together, these results provide a molecular framework of the temporal and training status-dependent exercise response that defines muscle plasticity in training. HIGHLIGHTSO_LIVery few persistent transcriptional events define the trained muscle. C_LIO_LIThe training status determines the acute exercise response. C_LIO_LIEpigenetic changes shape the transcriptional specification of trained muscle. C_LIO_LIAbsence of the key regulator PGC-1 causes suboptimal training adaptations. C_LI

physiology↗

bioRxiv2022

A network of cytosolic (co)chaperones promotes the biogenesis of mitochondrial signal-anchored outer membrane proteins

Signal-anchored (SA) proteins are anchored into the mitochondrial outer membrane (OM) via a single transmembrane segment at their N-terminus while the bulk of the proteins is facing the cytosol. These proteins are encoded by nuclear DNA, translated on cytosolic ribosomes, and are then targeted to the organelle and inserted into its OM by import factors. Recently, research on the insertion mechanisms of these proteins into the mitochondrial OM have gained a lot of attention. In contrast, the early cytosolic steps of their biogenesis are unresolved. Using various proteins from this category and a broad set of in vivo, in organello, and in vitro assays, we reconstituted the early steps of their biogenesis. We identified a subset of molecular (co)chaperones that interact with newly synthesized SA proteins, namely, Hsp70 and Hsp90 chaperones and co-chaperones from the Hsp40 family like Ydj1 and Sis1. These interactions were mediated by the hydrophobic transmembrane segments of the SA proteins. We further demonstrate that interfering with these interactions inhibits the biogenesis of SA proteins to varying extents. Finally, we could demonstrate direct interaction of peptides corresponding to the transmembrane segments of SA proteins with the (co)chaperones and reconstitute in vitro the transfer of such peptides from the Hsp70 chaperone to the mitochondrial Tom70 receptor. Collectively, this study unravels an array of cytosolic chaperones and mitochondrial import factors that facilitates the targeting and membrane integration of mitochondrial SA proteins.

biochemistry↗