Specific changes in mitochondrial lipidome alter mitochondrial proteome and increase the geroprotective efficiency of lithocholic acid in chronologically aging yeast
Bibliographic record
Abstract
// Anna Leonov 1 , Anthony Arlia-Ciommo 1 , Simon D. Bourque 1 , Olivia Koupaki 1 , Pavlo Kyryakov 1 , Paméla Dakik 1 , Mélissa McAuley 1 , Younes Medkour 1 , Karamat Mohammad 1 , Tamara Di Maulo 1 and Vladimir I. Titorenko 1 1 Department of Biology, Concordia University, Montreal, Quebec, Canada Correspondence to: Vladimir I. Titorenko, email: // Keywords : yeast, aging, mitochondria, mitochondrial lipidome, mitochondrial proteome, Gerotarget Received : February 20, 2017 Accepted : March 20, 2017 Published : March 31, 2017 Abstract We have previously found that exogenously added lithocholic acid delays yeast chronological aging. We demonstrated that lithocholic acid enters the yeast cell, is sorted to mitochondria, resides in both mitochondrial membranes, changes the relative concentrations of different membrane phospholipids, triggers changes in the concentrations of many mitochondrial proteins, and alters some key aspects of mitochondrial functionality. We hypothesized that the lithocholic acid-driven changes in mitochondrial lipidome may have a causal role in the remodeling of mitochondrial proteome, which may in turn alter the functional state of mitochondria to create a mitochondrial pattern that delays yeast chronological aging. Here, we test this hypothesis by investigating how the ups1Δ , ups2Δ and psd1Δ mutations that eliminate enzymes involved in mitochondrial phospholipid metabolism influence the mitochondrial lipidome. We also assessed how these mutations affect the mitochondrial proteome, influence mitochondrial functionality and impinge on the efficiency of aging delay by lithocholic acid. Our findings provide evidence that 1) lithocholic acid initially creates a distinct pro-longevity pattern of mitochondrial lipidome by proportionally decreasing phosphatidylethanolamine and cardiolipin concentrations to maintain equimolar concentrations of these phospholipids, and by increasing phosphatidic acid concentration; 2) this pattern of mitochondrial lipidome allows to establish a specific, aging-delaying pattern of mitochondrial proteome; and 3) this pattern of mitochondrial proteome plays an essential role in creating a distinctive, geroprotective pattern of mitochondrial functionality.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".