Polymerase Gamma Mutator (PolG) Mice Rely on Increased Glycolytic Flux for Energy Production
Bibliographic record
Abstract
PolG mice have reduced mitochondrial oxidative capacity secondary to systemic mitochondrial dysfunction, and subsequently show exercise intolerance. While the deleterious effects on oxidative capacity in the PolG mice have been clearly documented, assessment of a compensatory increase in anaerobic capacity in PolG mice is lacking. Thus, we sought to delineate the extent of glycolysis/gluconeogensis as a means of energy production in the PolG mice. PolG and wild‐type (WT) littermates were sacrificed at 10 mths of age, and blood/tissues were harvested. Primary dermal fibroblasts were also isolated from the animals and used to measure basal/maximal glycolysis using the Glycolysis stress test (Seahorse Bioscience). PolG mice displayed higher respiratory exchange ratio (RER) values, coupled with 55% lower locomotor activity compared to littermate WT mice (P < 0.05). PolG mice displayed resting hypoglycemia (3.4 mM), concomitantly with lower glucose levels throughout the GTT test as compared to WT, ~3‐fold higher PFK content, and elevated plasma lactate levels (>10 mM)(all P < 0.05). In vitro experiments provide further proof that PolG derived dermal fibroblasts have an ~50% higher basal and maximal rate of glycolysis vs . WT control. It is likely that the higher lactate content serves as substrate for the Cori cycle to generate glucose in the liver via gluconeogenesis. Indeed the mRNA content of two important gluconeogenic liver enzymes, G6P and PEPCK, was increased by ~3‐4x fold in the POLG mice compared to WT. Lactic acidosis and hypoglycemia have been associated with poor prognosis in a variety of mitochondrial diseases, and the presence in the PolG animals is a novel finding that warrants further attention. Funded by CIHR.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".