Biology subjects

Jamnick, N. A.

Publications and source records attributed to Jamnick, N. A..

3 recordsLinked to original sources

bioRxiv2025

GL261 glioblastoma induces delayed body weight gain and stunted skeletal muscle growth in young mice

IntroductionThe survival rate for children and adolescents has increased to over 85%. However, there is limited understanding of the impact of pediatric cancers on muscle development and physiology. Given that brain tumors alone account for 26% of all pediatric cancers, this study aimed to investigate the skeletal muscle consequences of tumor growth in young mice. MethodsC2C12 myotubes were co-cultured with GL261 murine glioblastoma cells to assess myotube size. GL261 cells were then injected subcutaneously into 4-week-old male C57BL/6J mice. Animals were euthanized 28 days post-GL261 implantation. Muscle function was tested in vivo and ex vivo. Muscle protein synthesis was measured via the SUnSET method, and gene/protein expression levels were assessed via Western blotting and qPCR. ResultsIn vitro, the C2C12 cultures exposed to GL261 exhibited myotube atrophy, consistent with a disrupted anabolic/catabolic balance. In vivo, carcass, heart, and fat mass were significantly reduced in the tumor-bearing mice. Skeletal muscle growth was impeded in the GL261 hosts, along with smaller muscle CSA. Both in vivo muscle torque and the ex vivo EDL muscle force were unchanged. At molecular level, the tumor hosts displayed reduced muscle protein synthesis and increased muscle protein ubiquitination, in disagreement with decreased muscle ubiquitin ligase mRNA expression. ConclusionsOverall, we showed that GL261 tumors impact the growth of pediatric mice by stunting skeletal muscle development, decreasing muscle mass, reducing muscle fiber size, diminishing muscle protein synthesis, and altering protein catabolism signaling.

cancer biology↗

bioRxiv2024

Sprint interval exercise disrupts mitochondrial ultrastructure driving a unique mitochondrial stress response and remodelling in humans

Exercise remains the most effective lifestyle intervention to remodel the mitochondrial network and to prevent most non-communicable diseases. Despite this, the molecular mechanisms by which different exercise prescriptions dictate mitochondrial remodelling are poorly understood in humans. Here, we show that, compared to moderate-intensity continuous exercise (MICE), sprint-interval exercise (SIE) - a known time-efficient high-intensity exercise - leads to mitochondrial stress and activates the mitochondrial unfolded protein response (UPRmt). The SIE-specific signature is characterized by a morphological and ultrastructural mitochondrial disturbance, concurrent with the activation of the integrated stress response (ISR) and mitochondrial quality control (MQC) pathways. When the respective exercises are repeated over time (8 weeks), our results demonstrate that moderate-intensity continuous training (MICT) and sprint-interval training (SIT) lead to a divergent mitochondrial remodelling. MICT elicits a mitochondrial adaptation characterized by an increase in markers of mitochondrial content, complex I activity, and enrichment of proteins involved in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) system. On the other hand, SIT leads to proteomic enrichment of pathways involved in mitochondrial 1-Carbon metabolism and protein quality control, concurrently with improvements in mitochondrial respiratory function. Lastly, we have identified COX7A2L as a divergently regulated protein across groups, significantly accumulating in III2+IV1 respiratory supercomplexes only following SIT. In conclusion, our study provides mechanistic insights on how SIE and MICE divergently impact the post-exercise mitochondrial signalling, and subsequent long-term mitochondrial remodelling following training. These findings provide a strong basis for targeted exercise prescription to modulate specific mitochondrial adaptations in human skeletal muscle.

molecular biology↗

bioRxiv2021

Multi-omics reveal intricate network of mitochondrial adaptations to training in human skeletal muscle

Mitochondrial defects are implicated in multiple diseases and aging. Exercise training is an accessible and inexpensive therapeutic intervention improving mitochondrial bioenergetics and quality of life. By combining a multi-omics approach with biochemical and in silico normalization, we removed the bias arising from the training-induced increase in human skeletal muscle mitochondrial content to unearth an intricate and previously undemonstrated network of differentially prioritized mitochondrial adaptations. We show that changes in hundreds of transcripts, proteins, and lipids are not stoichiometrically linked to the increase in mitochondrial content. We demonstrate that enhancing electron flow to oxidative phosphorylation (OXPHOS) is more important to improve ATP generation than increasing the abundance of the OXPHOS machinery, and that training-induced supercomplex formation does not confer enhancements in mitochondrial bioenergetics. Our study provides a new analytical approach allowing unbiased and in-depth investigations of training-induced mitochondrial adaptations, challenging our current understanding and calling for careful reinterpretation of previous findings.

cell biology↗