Phb1:Phb2 heterodimers in the mitochondria—beyond functional interdependence
Notice bibliographique
Résumé
Li et al. (1Li L. Martin-Levilain J. Jiménez-Sánchez C. Karaca M. Foti M. Martinou J.C. Maechler P. In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way.J. Biol. Chem. 2019; 294 (31285263): 12581-1259810.1074/jbc.RA119.007601Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar) showed that in vivo deletion of prohibitin-2 (Phb2) in hepatocytes (Hep-Phb2−/−) leads to impaired gluconeogenesis, reduced food intake, severe hypoglycemia, and, subsequently, poor survival. Phb2 and its homologous protein Phb1 form heterodimers in the mitochondria and are functionally interdependent (1Li L. Martin-Levilain J. Jiménez-Sánchez C. Karaca M. Foti M. Martinou J.C. Maechler P. In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way.J. Biol. Chem. 2019; 294 (31285263): 12581-1259810.1074/jbc.RA119.007601Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 2Supale S. Thorel F. Merkwirth C. Gjinovci A. Herrera P.L. Scorrano L. Meda P. Langer T. Maechler P. Loss of prohibitin induces mitochondrial damages altering beta-cell function and survival and is responsible for gradual diabetes development.Diabetes. 2013; 62 (23863811): 3488-349910.2337/db13-0152Crossref PubMed Scopus (75) Google Scholar3Merkwirth C. Martinelli P. Korwitz A. Morbin M. Brönneke H.S. Jordan S.D. Rugarli E.I. Langer T. Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to tau hyperphosphorylation and neurodegeneration.PLoS Genet. 2012; 8 (23144624): e100302110.1371/journal.pgen.1003021Crossref PubMed Scopus (132) Google Scholar). Consequently, the knockdown of either member leads to a parallel loss of the other member (1Li L. Martin-Levilain J. Jiménez-Sánchez C. Karaca M. Foti M. Martinou J.C. Maechler P. In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way.J. Biol. Chem. 2019; 294 (31285263): 12581-1259810.1074/jbc.RA119.007601Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar2Supale S. Thorel F. Merkwirth C. Gjinovci A. Herrera P.L. Scorrano L. Meda P. Langer T. Maechler P. Loss of prohibitin induces mitochondrial damages altering beta-cell function and survival and is responsible for gradual diabetes development.Diabetes. 2013; 62 (23863811): 3488-349910.2337/db13-0152Crossref PubMed Scopus (75) Google Scholar, 3Merkwirth C. Martinelli P. Korwitz A. Morbin M. Brönneke H.S. Jordan S.D. Rugarli E.I. Langer T. Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to tau hyperphosphorylation and neurodegeneration.PLoS Genet. 2012; 8 (23144624): e100302110.1371/journal.pgen.1003021Crossref PubMed Scopus (132) Google Scholar4Ko K.S. Tomasi M.L. Iglesias-Ara A. French B.A. French S.W. Ramani K. Lozano J.J. Oh P. He L. Stiles B.L. Li T.W. Yang H. Martínez-Chantar M.L. Mato J.M. Lu S.C. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.Hepatology. 2010; 52 (20890892): 2096-210810.1002/hep.23919Crossref PubMed Scopus (102) Google Scholar). Thus, it remains unclear whether or not Phb1 and Phb2 have protein-specific functions in the mitochondria. Of note, the hepatocyte-specific Phb1 knockout (Hep-Phb1−/−) mouse model has been developed (4Ko K.S. Tomasi M.L. Iglesias-Ara A. French B.A. French S.W. Ramani K. Lozano J.J. Oh P. He L. Stiles B.L. Li T.W. Yang H. Martínez-Chantar M.L. Mato J.M. Lu S.C. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.Hepatology. 2010; 52 (20890892): 2096-210810.1002/hep.23919Crossref PubMed Scopus (102) Google Scholar). Unfortunately, Li et al. did not acknowledge a single article published on the Hep-Phb1−/− mouse model (4Ko K.S. Tomasi M.L. Iglesias-Ara A. French B.A. French S.W. Ramani K. Lozano J.J. Oh P. He L. Stiles B.L. Li T.W. Yang H. Martínez-Chantar M.L. Mato J.M. Lu S.C. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.Hepatology. 2010; 52 (20890892): 2096-210810.1002/hep.23919Crossref PubMed Scopus (102) Google Scholar, 5Mavila N. Tang Y. Berlind J. Ramani K. Wang J. Mato J.M. Lu S.C. Prohibitin 1 acts as a negative regulator of wingless/integrated-β-catenin signaling in murine liver and human liver cancer cells.Hepatol. Commun. 2018; 2 (30556043): 1583-160010.1002/hep4.1257Crossref PubMed Scopus (10) Google Scholar6Fan W. Yang H. Liu T. Wang J. Li T.W. Mavila N. Tang Y. Yang J. Peng H. Tu J. Annamalai A. Noureddin M. Krishnan A. Gores G.J. Martínez-Chantar M.L. et al.Prohibitin 1 suppresses liver cancer tumorigenesis in mice and human hepatocellular and cholangiocarcinoma cells.Hepatology. 2017; 65 (27981602): 1249-126610.1002/hep.28964Crossref PubMed Scopus (40) Google Scholar). Similar to the Hep-Phb2−/− mice, the Hep-Phb1−/− mice display a parallel reduction in the levels of heterodimeric partners in hepatocytes and decreased body weight (1Li L. Martin-Levilain J. Jiménez-Sánchez C. Karaca M. Foti M. Martinou J.C. Maechler P. In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way.J. Biol. Chem. 2019; 294 (31285263): 12581-1259810.1074/jbc.RA119.007601Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 4Ko K.S. Tomasi M.L. Iglesias-Ara A. French B.A. French S.W. Ramani K. Lozano J.J. Oh P. He L. Stiles B.L. Li T.W. Yang H. Martínez-Chantar M.L. Mato J.M. Lu S.C. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.Hepatology. 2010; 52 (20890892): 2096-210810.1002/hep.23919Crossref PubMed Scopus (102) Google Scholar). However, the major liver-specific phenotypes of the Hep-Phb1−/− mice and the Hep-Phb2−/− mice are largely different, with distinctions like increased liver weight and the development of hepatocellular carcinoma in the former and reduced liver weight and severe hypoglycemia in the latter (1Li L. Martin-Levilain J. Jiménez-Sánchez C. Karaca M. Foti M. Martinou J.C. Maechler P. In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way.J. Biol. Chem. 2019; 294 (31285263): 12581-1259810.1074/jbc.RA119.007601Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 4Ko K.S. Tomasi M.L. Iglesias-Ara A. French B.A. French S.W. Ramani K. Lozano J.J. Oh P. He L. Stiles B.L. Li T.W. Yang H. Martínez-Chantar M.L. Mato J.M. Lu S.C. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.Hepatology. 2010; 52 (20890892): 2096-210810.1002/hep.23919Crossref PubMed Scopus (102) Google Scholar). Most importantly, the Hep-Phb1−/− mice survive much longer than the Hep-Phb2−/− mice (1Li L. Martin-Levilain J. Jiménez-Sánchez C. Karaca M. Foti M. Martinou J.C. Maechler P. In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way.J. Biol. Chem. 2019; 294 (31285263): 12581-1259810.1074/jbc.RA119.007601Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 4Ko K.S. Tomasi M.L. Iglesias-Ara A. French B.A. French S.W. Ramani K. Lozano J.J. Oh P. He L. Stiles B.L. Li T.W. Yang H. Martínez-Chantar M.L. Mato J.M. Lu S.C. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.Hepatology. 2010; 52 (20890892): 2096-210810.1002/hep.23919Crossref PubMed Scopus (102) Google Scholar) and other, cell type–specific knockout mouse models of Phb2 (2Supale S. Thorel F. Merkwirth C. Gjinovci A. Herrera P.L. Scorrano L. Meda P. Langer T. Maechler P. Loss of prohibitin induces mitochondrial damages altering beta-cell function and survival and is responsible for gradual diabetes development.Diabetes. 2013; 62 (23863811): 3488-349910.2337/db13-0152Crossref PubMed Scopus (75) Google Scholar, 3Merkwirth C. Martinelli P. Korwitz A. Morbin M. Brönneke H.S. Jordan S.D. Rugarli E.I. Langer T. Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to tau hyperphosphorylation and neurodegeneration.PLoS Genet. 2012; 8 (23144624): e100302110.1371/journal.pgen.1003021Crossref PubMed Scopus (132) Google Scholar). There could be a number of potential explanations for these differences; however, given that Phb1 and Phb2 function as the same heterodimeric complex in mitochondria, it is intriguing that they have such different phenotypes. It appears that the mitochondrial biology of Phb1 and Phb2 is more complex than simple interdependence. The development of the Hep-Phb2−/− mouse model along with the preexisting Hep-Phb1−/− mouse model provided an opportunity to initiate discussion around this stimulating question, which is completely missed by Li et al. (1Li L. Martin-Levilain J. Jiménez-Sánchez C. Karaca M. Foti M. Martinou J.C. Maechler P. In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way.J. Biol. Chem. 2019; 294 (31285263): 12581-1259810.1074/jbc.RA119.007601Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».