Biology subjects

Gouspillou, G.

Publications and source records attributed to Gouspillou, G..

2 recordsLinked to original sources

bioRxiv2021

Dynamic behavior of cell-free mitochondrial DNA in human saliva

Mitochondria contain their own genome that can be released in multiple biofluids such as blood and cerebrospinal fluid, as cell-free mitochondrial DNA (cf-mtDNA). In clinical studies, single measures of blood cf-mtDNA predict mortality, and higher cf-mtDNA levels are associated with mental and physical stress. However, the dynamics of cf-mtDNA has not been defined, and whether it can be measured non-invasively like other neuroendocrine markers in saliva has not been examined. Here we report cf-mtDNA in human saliva and establish its natural within-person dynamic behavior across multiple weeks. In a small proof-of-principle cohort of healthy adults, we first develop an approach to rapidly quantify salivary cf-mtDNA without DNA extraction, and demonstrate the existence of saliva cf-mtDNA. We then deploy this approach to perform an intensive repeated-measures analysis of two healthy men studied at 4 daily timepoints over 53-60 consecutive days (n=212-220 observations each) with parallel measures of steroid hormones, self-reported daily mood, and health-related behaviors. Salivary cf-mtDNA exhibited a robust awakening response reaching up to two orders of magnitude 30-45 minutes after awakening, varied from day-to-day, and moderately correlated with the cortisol awakening response. No consistent association with self-reported daily mood/health-related behaviors were found, although this requires further examination in more extensive studies. Dynamic variation in cf-mtDNA was inversely related with salivary interleukin 6 (IL6), inconsistent with a pro-inflammatory effect of salivary cf-mtDNA. The highly dynamic behavior of salivary cf-mtDNA opens the door to non-invasive studies examining the relevance of mtDNA signaling in relation to human health.

molecular biology↗

bioRxiv2021

Role of autophagy in sepsis-induced skeletal muscle dysfunction, whole-body metabolism, and survival

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences and adverse outcomes. Autophagy is a stress-induced degradative process essential to cell survival. Recent studies have demonstrated that sepsis triggers sustained induction of autophagy in skeletal muscles, although the impact of this enhanced autophagy on sepsis-induced muscle dysfunction remains unclear. Atg7 is an autophagy gene that plays a major role in autophagosome formation. Using an inducible and muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated the functional importance of skeletal muscle autophagy in sepsis. Sepsis was induced using cecal ligation and perforation (CLP) with a sham operation serving as a control. Atg7iSkM-KO mice exhibited a more severe phenotype in response to sepsis, marked by severe muscle wasting and contractile dysfunction, hypoglycemia, higher ketone levels and a decreased in survival as compared to mice with intact Atg7. Several genes that encode 26S proteasome subunits were upregulated, suggesting that activation of the ubiquitin-proteasome system is responsible for the severe muscle atrophy that was seen in these mice. Sepsis and Atg7 deletion resulted in the accumulation of mitochondrial dysfunction, although sepsis did not further worsen mitochondrial dysfunction in Atg7iSkM-KO mice. Overall, our study demonstrates that autophagy inactivation in skeletal muscles triggers significant worsening of sepsis-induced contractile and metabolic dysfunctions and negatively impacts survival. Induction of autophagy in skeletal muscles in response to sepsis thus represents a protective mechanism.

cell biology↗