ORCID Profile
0000-0002-7783-0278
Current Organisations
St Vincent's Clinic
,
Garvan Institute of Medical Research
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 06-01-2021
DOI: 10.1113/JP279411
Abstract: Mitochondria are dynamic organelles, intricately designed to meet cellular energy requirements. To accommodate alterations in energy demand, mitochondria have a high degree of plasticity, changing in response to transient activation of numerous stress‐related pathways. This adaptive response is particularly relevant in highly metabolic tissues such as skeletal muscle, where mitochondria support numerous biological processes related to metabolism, growth and regeneration. Aerobic exercise is a potent stimulus for skeletal muscle remodelling, leading to alterations in substrate utilisation, fibre‐type composition and performance. Underlying these physiological responses is a change in mitochondrial quality control (MQC), a term encompassing the co‐ordination of mitochondrial synthesis (biogenesis), remodelling (dynamics) and degradation (mitophagy) pathways. Understanding of MQC in skeletal muscle and the regulatory role of aerobic exercise of this process are rapidly advancing, as are the molecular techniques allowing the study of MQC in vivo . Given the emerging link between MQC and the onset of numerous non‐communicable diseases, understanding the molecular regulation of MQC, and the role of aerobic exercise in this process, will have substantial future impact on therapeutic approaches to manipulate MQC and maintain mitochondrial function across health span. image
Publisher: Bioscientifica
Date: 05-2021
DOI: 10.1530/JOE-20-0233
Abstract: Vitamin D deficiency is associated with symptoms of skeletal muscle myopathy including muscle weakness and fatigue. Recently, vitamin D-related metabolites have been linked to the maintenance of mitochondrial function within skeletal muscle. However, current evidence is limited to in vitro models and the effects of diet-induced vitamin D deficiency upon skeletal muscle mitochondrial function in vivo have received little attention. In order to examine the role of vitamin D in the maintenance of mitochondrial function in vivo , we utilised an established model of diet-induced vitamin D deficiency in C57BL/6J mice. Mice were either fed a control diet (2200 IU/kg i.e. vitamin D replete) or a vitamin D-deplete (0 IU/kg) diet for periods of 1, 2 and 3 months. Gastrocnemius muscle mitochondrial function and ADP sensitivity were assessed via high-resolution respirometry and mitochondrial protein content via immunoblotting. As a result of 3 months of diet-induced vitamin D deficiency, respiration supported via complex I + II (CI + II P ) and the electron transport chain (ETC) were 35 and 37% lower when compared to vitamin D-replete mice ( P 0.05). Despite functional alterations, citrate synthase activity, AMPK phosphorylation, mitofilin, OPA1 and ETC subunit protein content remained unchanged in response to dietary intervention ( P 0.05). In conclusion, we report that 3 months of diet-induced vitamin D deficiency reduced skeletal muscle mitochondrial respiration in C57BL/6J mice. Our data, when combined with previous in vitro observations, suggest that vitamin D-mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Wiley
Date: 29-01-2021
DOI: 10.1113/JP280825
Publisher: Proceedings of the National Academy of Sciences
Date: 24-02-2021
Abstract: Duchenne muscular dystrophy (DMD) is a fatal degenerative disease without a cure. Current standard pharmacological treatment is corticosteroids. Their prolonged use is associated with several undesirable side effects. Using Caenorhabditis elegans , we have identified pharmacological treatments that supplement hydrogen sulfide (H 2 S). One, sodium GYY4137, largely acts like prednisone to improve neuromuscular health the other, AP39, targets H 2 S delivery to mitochondria. As these are not steroids, they are unlikely to produce steroid-induced side effects. Additionally, as DMD mice show a decline in total sulfide, our results pave the way for evaluation of cellular and/or mitochondrial H 2 S in DMD pathology and warrant further investigation of selective H 2 S delivery approaches in mdx mice and/or higher animal models of DMD.
Publisher: Elsevier BV
Date: 09-2021
No related grants have been discovered for Ashleigh Philp.