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A metabolite sensor subunit of the Atg1/ULK complex regulates selective autophagy.
Gross AS, Ghillebert R, Schuetter M, Reinartz E, Rowland A, Bishop BC, Stumpe M, Dengjel J, Graef M. Gross AS, et al. Among authors: graef m. Nat Cell Biol. 2024 Mar;26(3):366-377. doi: 10.1038/s41556-024-01348-4. Epub 2024 Feb 5. Nat Cell Biol. 2024. PMID: 38316984 Free PMC article.
Cells convert complex metabolic information into stress-adapted autophagy responses. Canonically, multilayered protein kinase networks converge on the conserved Atg1/ULK kinase complex (AKC) to induce non-selective and selective forms of autophagy in response to met …
Cells convert complex metabolic information into stress-adapted autophagy responses. Canonically, multilayered protein kinase network …
Parallel phospholipid transfer by Vps13 and Atg2 determines autophagosome biogenesis dynamics.
Dabrowski R, Tulli S, Graef M. Dabrowski R, et al. Among authors: graef m. J Cell Biol. 2023 Jul 3;222(7):e202211039. doi: 10.1083/jcb.202211039. Epub 2023 Apr 28. J Cell Biol. 2023. PMID: 37115156 Free PMC article.
During autophagy, rapid membrane assembly expands small phagophores into large double-membrane autophagosomes. ...
During autophagy, rapid membrane assembly expands small phagophores into large double-membrane autophagosomes. ...
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1).
Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, Adamopoulos IE, Adeli K, Adolph TE, Adornetto A, Aflaki E, Agam G, Agarwal A, Aggarwal BB, Agnello M, Agostinis P, Agrewala JN, Agrotis A, Aguilar PV, Ahmad ST, Ahmed ZM, Ahumada-Castro U, Aits S, Aizawa S, Akkoc Y, Akoumianaki T, Akpinar HA, Al-Abd AM, Al-Akra L, Al-Gharaibeh A, Alaoui-Jamali MA, Alberti S, Alcocer-Gómez E, Alessandri C, Ali M, Alim Al-Bari MA, Aliwaini S, Alizadeh J, Almacellas E, Almasan A, Alonso A, Alonso GD, Altan-Bonnet N, Altieri DC, Álvarez ÉMC, Alves S, Alves da Costa C, Alzaharna MM, Amadio M, Amantini C, Amaral C, Ambrosio S, Amer AO, Ammanathan V, An Z, Andersen SU, Andrabi SA, Andrade-Silva M, Andres AM, Angelini S, Ann D, Anozie UC, Ansari MY, Antas P, Antebi A, Antón Z, Anwar T, Apetoh L, Apostolova N, Araki T, Araki Y, Arasaki K, Araújo WL, Araya J, Arden C, Arévalo MA, Arguelles S, Arias E, Arikkath J, Arimoto H, Ariosa AR, Armstrong-James D, Arnauné-Pelloquin L, Aroca A, Arroyo DS, Arsov I, Artero R, Asaro DML, Aschner M, Ashrafizadeh M, Ashur-Fabian O, Atanasov AG, Au AK, Auberger P, Auner HW, Aurelian L, Autelli R… See abstract for full author list ➔ Klionsky DJ, et al. Among authors: graef m. Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280. Epub 2021 Feb 8. Autophagy. 2021. PMID: 33634751 Free PMC article.
Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukary …
Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite num …
Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation.
Sawa-Makarska J, Baumann V, Coudevylle N, von Bülow S, Nogellova V, Abert C, Schuschnig M, Graef M, Hummer G, Martens S. Sawa-Makarska J, et al. Among authors: graef m. Science. 2020 Sep 4;369(6508):eaaz7714. doi: 10.1126/science.aaz7714. Science. 2020. PMID: 32883836 Free PMC article.
Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)-containing vesicles that are required for autophagy machinery assembly but do not supply the bulk of the autophagosomal membrane. . …
Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9 …
Stress eating: Autophagy targets nuclear pore complexes.
Gross AS, Graef M. Gross AS, et al. Among authors: graef m. J Cell Biol. 2020 Jul 6;219(7):e202006007. doi: 10.1083/jcb.202006007. J Cell Biol. 2020. PMID: 32584933 Free PMC article.
Cell Biol.https://doi.org/10.1083/jcb.201910063) describe the targeted degradation of nuclear pore complexes (NPCs) by selective autophagy, providing insight into the mechanisms of turnover for individual nucleoporins and entire NPCs....
Cell Biol.https://doi.org/10.1083/jcb.201910063) describe the targeted degradation of nuclear pore complexes (NPCs) by selective autophag
Recent advances in the understanding of autophagosome biogenesis.
Graef M. Graef M. F1000Res. 2020 Mar 26;9:F1000 Faculty Rev-212. doi: 10.12688/f1000research.22111.1. eCollection 2020. F1000Res. 2020. PMID: 32266060 Free PMC article. Review.
Autophagy is a conserved catabolic process critical for cell homeostasis with broad implications for aging and age-associated diseases. A defining feature of autophagy is the de novo formation of a specialized transient organelle, the double-membrane autophagosome.
Autophagy is a conserved catabolic process critical for cell homeostasis with broad implications for aging and age-associated disease
Localized de novo phospholipid synthesis drives autophagosome biogenesis.
Schütter M, Graef M. Schütter M, et al. Among authors: graef m. Autophagy. 2020 Apr;16(4):770-771. doi: 10.1080/15548627.2020.1725379. Epub 2020 Feb 6. Autophagy. 2020. PMID: 32013690 Free PMC article.
During (macro)autophagy, cells form transient organelles, termed autophagosomes, to target a broad spectrum of substrates for degradation critical to cellular and organismal health. ...In summary, our work uncovers molecular principles of how cells coordinate phospholipid …
During (macro)autophagy, cells form transient organelles, termed autophagosomes, to target a broad spectrum of substrates for degrada …
Local Fatty Acid Channeling into Phospholipid Synthesis Drives Phagophore Expansion during Autophagy.
Schütter M, Giavalisco P, Brodesser S, Graef M. Schütter M, et al. Among authors: graef m. Cell. 2020 Jan 9;180(1):135-149.e14. doi: 10.1016/j.cell.2019.12.005. Epub 2019 Dec 26. Cell. 2020. PMID: 31883797 Free article.
Autophagy is a conserved catabolic homeostasis process central for cellular and organismal health. ...Indeed, the first committed steps of de novo phospholipid synthesis at the ER, which forms stable contacts with nascent autophagosomes, are essential for autophagy.
Autophagy is a conserved catabolic homeostasis process central for cellular and organismal health. ...Indeed, the first committed ste
Mechanisms of Autophagy in Metabolic Stress Response.
Gross AS, Graef M. Gross AS, et al. Among authors: graef m. J Mol Biol. 2020 Jan 3;432(1):28-52. doi: 10.1016/j.jmb.2019.09.005. Epub 2019 Oct 15. J Mol Biol. 2020. PMID: 31626805 Review.
Autophagy is a highly conserved catabolic pathway critical for stress responses and the maintenance of cellular homeostasis. ...With an emphasis on findings in the yeast system, we will describe the emerging principles underlying the regulation of autophagy substrat
Autophagy is a highly conserved catabolic pathway critical for stress responses and the maintenance of cellular homeostasis. ...With
Relaxed Selection Limits Lifespan by Increasing Mutation Load.
Cui R, Medeiros T, Willemsen D, Iasi LNM, Collier GE, Graef M, Reichard M, Valenzano DR. Cui R, et al. Among authors: graef m. Cell. 2019 Jul 11;178(2):385-399.e20. doi: 10.1016/j.cell.2019.06.004. Epub 2019 Jun 27. Cell. 2019. PMID: 31257025 Free article.
Autophagy determines mtDNA copy number dynamics during starvation.
Medeiros TC, Graef M. Medeiros TC, et al. Among authors: graef m. Autophagy. 2019 Jan;15(1):178-179. doi: 10.1080/15548627.2018.1532263. Epub 2018 Oct 13. Autophagy. 2019. PMID: 30301401 Free PMC article.
Derived from bacterial ancestors, mitochondria have maintained their own albeit strongly reduced genome, mitochondrial DNA (mtDNA), which encodes for a small and highly specialized set of genes. ...The balance of the 2 modes of Mip1/POLG and thus mtDNA copy number dynamics …
Derived from bacterial ancestors, mitochondria have maintained their own albeit strongly reduced genome, mitochondrial DNA (mtDNA), w …
Membrane tethering by the autophagy ATG2A-WIPI4 complex.
Graef M. Graef M. Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):10540-10541. doi: 10.1073/pnas.1814759115. Epub 2018 Oct 1. Proc Natl Acad Sci U S A. 2018. PMID: 30275332 Free PMC article. No abstract available.
Autophagy balances mtDNA synthesis and degradation by DNA polymerase POLG during starvation.
Medeiros TC, Thomas RL, Ghillebert R, Graef M. Medeiros TC, et al. Among authors: graef m. J Cell Biol. 2018 May 7;217(5):1601-1611. doi: 10.1083/jcb.201801168. Epub 2018 Mar 8. J Cell Biol. 2018. PMID: 29519802 Free PMC article.
Here we found that DNA synthesis and degradation by mtDNA polymerase gamma (POLG) dynamically controlled mtDNA copy number in starving yeast cells dependent on metabolic homeostasis provided by autophagy. Specifically, the continuous mtDNA synthesis by POLG in starving wil …
Here we found that DNA synthesis and degradation by mtDNA polymerase gamma (POLG) dynamically controlled mtDNA copy number in starving yeast …
Lipid droplet-mediated lipid and protein homeostasis in budding yeast.
Graef M. Graef M. FEBS Lett. 2018 Apr;592(8):1291-1303. doi: 10.1002/1873-3468.12996. Epub 2018 Feb 16. FEBS Lett. 2018. PMID: 29397034 Free PMC article. Review.
Our view on this unique organelle has evolved from a simple fat deposit to a highly dynamic and functionally diverse hub-one that mediates the buffering of fatty acid stress and the adaptive reshaping of lipid metabolism to promote membrane and organelle homeostasis and the integ …
Our view on this unique organelle has evolved from a simple fat deposit to a highly dynamic and functionally diverse hub-one that mediates t …
Autophagy regulation depends on ER homeostasis controlled by lipid droplets.
Velázquez AP, Graef M. Velázquez AP, et al. Among authors: graef m. Autophagy. 2016 Aug 2;12(8):1409-10. doi: 10.1080/15548627.2016.1190074. Epub 2016 May 31. Autophagy. 2016. PMID: 27245853 Free PMC article.
Macroautophagy (hereafter autophagy) is a highly conserved homeostasis and quality control process critically linked to neurodegeneration, metabolic diseases, cancer, and aging. A key feature of autophagy is the de novo formation of autophagosomes, double-membrane v …
Macroautophagy (hereafter autophagy) is a highly conserved homeostasis and quality control process critically linked to neurodegenera …
Lipid droplet-mediated ER homeostasis regulates autophagy and cell survival during starvation.
Velázquez AP, Tatsuta T, Ghillebert R, Drescher I, Graef M. Velázquez AP, et al. Among authors: graef m. J Cell Biol. 2016 Mar 14;212(6):621-31. doi: 10.1083/jcb.201508102. Epub 2016 Mar 7. J Cell Biol. 2016. PMID: 26953354 Free PMC article.
Recent studies suggest that LDs function as direct lipid sources for autophagy, a central catabolic process in homeostasis and stress response. Here, we demonstrate that LDs are dispensable as a membrane source for autophagy, but fulfill critical functions for endop …
Recent studies suggest that LDs function as direct lipid sources for autophagy, a central catabolic process in homeostasis and stress …
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM, Ait-Si-Ali S, Akematsu T, Akporiaye ET, Al-Rubeai M, Albaiceta GM, Albanese C, Albani D, Albert ML, Aldudo J, Algül H, Alirezaei M, Alloza I, Almasan A, Almonte-Beceril M, Alnemri ES, Alonso C, Altan-Bonnet N, Altieri DC, Alvarez S, Alvarez-Erviti L, Alves S, Amadoro G, Amano A, Amantini C, Ambrosio S, Amelio I, Amer AO, Amessou M, Amon A, An Z, Anania FA, Andersen SU, Andley UP, Andreadi CK, Andrieu-Abadie N, Anel A, Ann DK, Anoopkumar-Dukie S, Antonioli M, Aoki H, Apostolova N, Aquila S, Aquilano K, Araki K, Arama E, Aranda A, Araya J, Arcaro A, Arias E, Arimoto H, Ariosa AR, Armstrong JL, Arnould T, Arsov I, Asanuma K, Askanas V, Asselin E, Atarashi R, Atherton SS, Atkin JD, Attardi LD, Auberger P, Auburger G, Aurelian L, Autelli R, Avagliano L, Avantaggiati ML, Avrahami L, Awale S, Azad N, Bachetti T, Backer JM, Bae DH, Bae JS, Bae ON, Bae SH, Baehrecke EH, Baek SH, Baghdiguian S, Bagniewska-Zadworna A, Bai H, Bai J, Bai XY, Bailly Y, Balaji KN, … See abstract for full author list ➔ Klionsky DJ, et al. Among authors: graef m. Autophagy. 2016;12(1):1-222. doi: 10.1080/15548627.2015.1100356. Autophagy. 2016. PMID: 26799652 Free PMC article. No abstract available.
TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.
Vlahakis A, Graef M, Nunnari J, Powers T. Vlahakis A, et al. Among authors: graef m. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10586-91. doi: 10.1073/pnas.1406305111. Epub 2014 Jul 7. Proc Natl Acad Sci U S A. 2014. PMID: 25002487 Free PMC article.
Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2 …
Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through th …
ER exit sites are physical and functional core autophagosome biogenesis components.
Graef M, Friedman JR, Graham C, Babu M, Nunnari J. Graef M, et al. Mol Biol Cell. 2013 Sep;24(18):2918-31. doi: 10.1091/mbc.E13-07-0381. Epub 2013 Jul 31. Mol Biol Cell. 2013. PMID: 23904270 Free PMC article.
Autophagy is a central homeostasis and stress response pathway conserved in all eukaryotes. One hallmark of autophagy is the de novo formation of autophagosomes. These double-membrane vesicular structures form around and deliver cargo for degradation by the vacuole/
Autophagy is a central homeostasis and stress response pathway conserved in all eukaryotes. One hallmark of autophagy is the d
Endoplasmic reticulum-associated mitochondria-cortex tether functions in the distribution and inheritance of mitochondria.
Lackner LL, Ping H, Graef M, Murley A, Nunnari J. Lackner LL, et al. Among authors: graef m. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E458-67. doi: 10.1073/pnas.1215232110. Epub 2013 Jan 22. Proc Natl Acad Sci U S A. 2013. PMID: 23341591 Free PMC article.
Our data indicate that Num1, together with Mdm36, forms a physical tether that robustly anchors mitochondria to the cell cortex but plays no direct role in mitochondrial division. ...We find that the cortical endoplasmic reticulum (ER) also is a constituent of the Num1 …
Our data indicate that Num1, together with Mdm36, forms a physical tether that robustly anchors mitochondria to the cell cortex but p …
A role for mitochondria in autophagy regulation.
Graef M, Nunnari J. Graef M, et al. Autophagy. 2011 Oct;7(10):1245-6. doi: 10.4161/auto.7.10.16508. Epub 2011 Oct 1. Autophagy. 2011. PMID: 21613823
Autophagy functions in both cellular homeostasis and in quality control in the selective removal of dysfunctional mitochondria. A current working model in the field is that impaired autophagy results in a cell-damaging accumulation of dysfunctional mitocho
Autophagy functions in both cellular homeostasis and in quality control in the selective removal of dysfunctional mitochondria
Mitochondria regulate autophagy by conserved signalling pathways.
Graef M, Nunnari J. Graef M, et al. EMBO J. 2011 Jun 1;30(11):2101-14. doi: 10.1038/emboj.2011.104. Epub 2011 Apr 5. EMBO J. 2011. PMID: 21468027 Free PMC article.
Autophagy is a conserved degradative process that is crucial for cellular homeostasis and cellular quality control via the selective removal of subcellular structures such as mitochondria. We demonstrate that a regulatory link exists between mitochondrial function a
Autophagy is a conserved degradative process that is crucial for cellular homeostasis and cellular quality control via the selective
Substrate specific consequences of central pore mutations in the i-AAA protease Yme1 on substrate engagement.
Graef M, Langer T. Graef M, et al. J Struct Biol. 2006 Oct;156(1):101-8. doi: 10.1016/j.jsb.2006.01.009. Epub 2006 Feb 21. J Struct Biol. 2006. PMID: 16527490
Two membrane-bound ATP-dependent AAA proteases conduct protein quality surveillance in the inner membrane of mitochondria and control crucial steps during mitochondrial biogenesis. ...
Two membrane-bound ATP-dependent AAA proteases conduct protein quality surveillance in the inner membrane of mitochondria and control …