Consequences of Cytochrome <i>c</i> Oxidase Assembly Defects for the Yeast Stationary Phase
Bibliographic record
Abstract
Functional assembly of cytochrome c oxidase (COX) is essential for an intact mitochondrial respiratory chain, although the consequences of a loss of assembled COX at yeast stationary phase remain largely unexplored. Stationary phase cultures are a good model for terminally differentiated cells in humans, such as neurons. Our goal is to define the physiological changes in mitochondrial respiration and oxidative stress between exponential and stationary phases in a respiratory competent strain and a set of COX assembly mutants with defects in a variety of aspects related to enzyme assembly. These results further our understanding of mitochondrial changes in terminally differentiated cells and aging cells. In this study, we show that a wild‐type respiratory competent yeast strain at stationary phase is characterized by a decreased oxidative capacity, as seen by a reduction in the amount of assembled COX, which is supported by a decrease in protein levels of several COX assembly factors. Wild‐type cells also have a disrupted mitochondrial reticulum during stationary phase. Loss of assembled COX results in the decreased abundance of many mitochondrial proteins at stationary phase, which we show is likely due to decreased membrane potential and changes in mitophagy. In addition to an altered mitochondrial proteome, COX assembly mutants display unexpected changes in markers of cellular oxidative stress at stationary phase. Specifically, differences in distribution of Sod1 between exponential and stationary phases give insight on location of reactive oxygen species (ROS) in the cell. Our results suggest that mitochondria may not be a major source of ROS at stationary phase in cells lacking an intact respiratory chain. Overall, we have identified fundamental differences between exponential and stationary phase mitochondria in respiratory competent yeast and have defined two distinct phenotypes, decreased levels of mitochondrial proteins and less mitochondrial oxidative damage, in cells with a defective respiratory chain. These findings suggest that COX deficiencies are associated with broader cellular phenotypes in terminally differentiated cells in humans. Support or Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".