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Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48.

Moreno-Beltrán B, Guerra-Castellano A, Díaz-Quintana A, Del Conte R, García-Mauriño SM, Díaz-Moreno S, González-Arzola K, Santos-Ocaña C, Velázquez-Campoy A, De la Rosa MA, Turano P, Díaz-Moreno I
Proc Natl Acad Sci U S A 114 E3041-E3050 (2017)
Cited: 34 times
EuropePMC logo PMID: 28348229

Abstract

Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation-in particular, at tyrosine 48-is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methyl-l-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects.

Articles - 2n3y mentioned but not cited (3)

  1. Quercetin conjugated with superparamagnetic iron oxide nanoparticles improves learning and memory better than free quercetin via interacting with proteins involved in LTP. Amanzadeh E, Esmaeili A, Abadi REN, Kazemipour N, Pahlevanneshan Z, Beheshti S. Sci Rep 9 6876 (2019)
  2. Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48. Moreno-Beltrán B, Guerra-Castellano A, Díaz-Quintana A, Del Conte R, García-Mauriño SM, Díaz-Moreno S, González-Arzola K, Santos-Ocaña C, Velázquez-Campoy A, De la Rosa MA, Turano P, Díaz-Moreno I. Proc Natl Acad Sci U S A 114 E3041-E3050 (2017)
  3. Exploring protein phosphorylation by combining computational approaches and biochemical methods. Pérez-Mejías G, Velázquez-Cruz A, Guerra-Castellano A, Baños-Jaime B, Díaz-Quintana A, González-Arzola K, Ángel De la Rosa M, Díaz-Moreno I. Comput Struct Biotechnol J 18 1852-1863 (2020)


Reviews citing this publication (11)

  1. HIGD-Driven Regulation of Cytochrome c Oxidase Biogenesis and Function. Timón-Gómez A, Bartley-Dier EL, Fontanesi F, Barrientos A. Cells 9 E2620 (2020)
  2. Mitochondrial Kinases and the Role of Mitochondrial Protein Phosphorylation in Health and Disease. Kotrasová V, Keresztesová B, Ondrovičová G, Bauer JA, Havalová H, Pevala V, Kutejová E, Kunová N. Life (Basel) 11 82 (2021)
  3. Tissue-specific regulation of cytochrome c by post-translational modifications: respiration, the mitochondrial membrane potential, ROS, and apoptosis. Kalpage HA, Bazylianska V, Recanati MA, Fite A, Liu J, Wan J, Mantena N, Malek MH, Podgorski I, Heath EI, Vaishnav A, Edwards BF, Grossman LI, Sanderson TH, Lee I, Hüttemann M. FASEB J. 33 1540-1553 (2019)
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  5. Mitochondrial cytochrome c shot towards histone chaperone condensates in the nucleus. González-Arzola K, Guerra-Castellano A, Rivero-Rodríguez F, Casado-Combreras MÁ, Pérez-Mejías G, Díaz-Quintana A, Díaz-Moreno I, De la Rosa MA. FEBS Open Bio 11 2418-2440 (2021)
  6. Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of Cytochrome c and Cardiolipin. Díaz-Quintana A, Pérez-Mejías G, Guerra-Castellano A, De la Rosa MA, Díaz-Moreno I. Oxid Med Cell Longev 2020 6813405 (2020)
  7. Post-Translational Modifications of Cytochrome c in Cell Life and Disease. Guerra-Castellano A, Márquez I, Pérez-Mejías G, Díaz-Quintana A, De la Rosa MA, Díaz-Moreno I. Int J Mol Sci 21 E8483 (2020)
  8. Cytochrome c: Surfing Off of the Mitochondrial Membrane on the Tops of Complexes III and IV. Pérez-Mejías G, Guerra-Castellano A, Díaz-Quintana A, De la Rosa MA, Díaz-Moreno I. Comput Struct Biotechnol J 17 654-660 (2019)
  9. In Situ Spectroelectrochemical Investigations of Electrode-Confined Electron-Transferring Proteins and Redox Enzymes. Murgida DH. ACS Omega 6 3435-3446 (2021)
  10. Mitochondrial Factors in the Cell Nucleus. González-Arzola K, Díaz-Quintana A. Int J Mol Sci 24 13656 (2023)
  11. Phosphorylation of OXPHOS Machinery Subunits: Functional Implications in Cell Biology and Disease. Castellanos E, Lanning NJ. Yale J Biol Med 92 523-531 (2019)

Articles citing this publication (20)

  1. Cytochrome c phosphorylation: Control of mitochondrial electron transport chain flux and apoptosis. Kalpage HA, Wan J, Morse PT, Zurek MP, Turner AA, Khobeir A, Yazdi N, Hakim L, Liu J, Vaishnav A, Sanderson TH, Recanati MA, Grossman LI, Lee I, Edwards BFP, Hüttemann M. Int J Biochem Cell Biol 121 105704 (2020)
  2. Lysine 53 Acetylation of Cytochrome c in Prostate Cancer: Warburg Metabolism and Evasion of Apoptosis. Bazylianska V, Kalpage HA, Wan J, Vaishnav A, Mahapatra G, Turner AA, Chowdhury DD, Kim K, Morse PT, Lee I, Brunzelle JS, Polin L, Subedi P, Heath EI, Podgorski I, Marcus K, Edwards BFP, Hüttemann M. Cells 10 802 (2021)
  3. Nitric oxide mediated inhibition of antigen presentation from DCs to CD4+ T cells in cancer and measurement of STAT1 nitration. Markowitz J, Wang J, Vangundy Z, You J, Yildiz V, Yu L, Foote IP, Branson OE, Stiff AR, Brooks TR, Biesiadecki B, Olencki T, Tridandapani S, Freitas MA, Papenfuss T, Phelps MA, Carson WE. Sci Rep 7 15424 (2017)
  4. Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria. Guerra-Castellano A, Díaz-Quintana A, Pérez-Mejías G, Elena-Real CA, González-Arzola K, García-Mauriño SM, De la Rosa MA, Díaz-Moreno I. Proc. Natl. Acad. Sci. U.S.A. 115 7955-7960 (2018)
  5. Cytochrome c autocatalyzed carbonylation in the presence of hydrogen peroxide and cardiolipins. Barayeu U, Lange M, Méndez L, Arnhold J, Shadyro OI, Fedorova M, Flemmig J. J. Biol. Chem. 294 1816-1830 (2019)
  6. Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition. Elena-Real CA, Díaz-Quintana A, González-Arzola K, Velázquez-Campoy A, Orzáez M, López-Rivas A, Gil-Caballero S, De la Rosa MÁ, Díaz-Moreno I. Cell Death Dis 9 365 (2018)
  7. Structural and functional insights into lysine acetylation of cytochrome c using mimetic point mutants. Márquez I, Pérez-Mejías G, Guerra-Castellano A, Olloqui-Sariego JL, Andreu R, Calvente JJ, De la Rosa MA, Díaz-Moreno I. FEBS Open Bio 11 3304-3323 (2021)
  8. A FRET-based respirasome assembly screen identifies spleen tyrosine kinase as a target to improve muscle mitochondrial respiration and exercise performance in mice. Kobayashi A, Azuma K, Takeiwa T, Kitami T, Horie K, Ikeda K, Inoue S. Nat Commun 14 312 (2023)
  9. Analogs of imine resveratrol alleviate oxidative stress-induced neurotoxicity in PC12 cells via activation of Nrf2. Zhang Y, Wang Z, Yang J, He Y, Wan H, Li C. FEBS Open Bio (2021)
  10. Control of Mitochondrial Electron Transport Chain Flux and Apoptosis by Retinoic Acid: Raman Imaging In Vitro Human Bronchial and Lung Cancerous Cells. Abramczyk H, Surmacki JM. Cancers (Basel) 15 4535 (2023)
  11. Cytochrome c in cancer therapy and prognosis. Pessoa J. Biosci Rep 42 BSR20222171 (2022)
  12. Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle. Morse PT, Pérez-Mejías G, Wan J, Turner AA, Márquez I, Kalpage HA, Vaishnav A, Zurek MP, Huettemann PP, Kim K, Arroum T, De la Rosa MA, Chowdhury DD, Lee I, Brunzelle JS, Sanderson TH, Malek MH, Meierhofer D, Edwards BFP, Díaz-Moreno I, Hüttemann M. Nat Commun 14 4166 (2023)
  13. De novo sequencing and construction of a unique antibody for the recognition of alternative conformations of cytochrome c in cells. Tomasina F, Martínez J, Zeida A, Chiribao ML, Demicheli V, Correa A, Quijano C, Castro L, Carnahan RH, Vinson P, Goff M, Cooper T, McDonald WH, Castellana N, Hannibal L, Morse PT, Wan J, Hüttemann M, Jemmerson R, Piacenza L, Radi R. Proc Natl Acad Sci U S A 119 e2213432119 (2022)
  14. Distal Unfolding of Ferricytochrome c Induced by the F82K Mutation. Lalli D, Rosa C, Allegrozzi M, Turano P. Int J Mol Sci 21 (2020)
  15. Exploring plasma metabolomic changes in sepsis: a clinical matching study based on gas chromatography-mass spectrometry. Lin SH, Fan J, Zhu J, Zhao YS, Wang CJ, Zhang M, Xu F. Ann Transl Med 8 1568 (2020)
  16. Genetically Encoded Fluorescent Probe for Detection of Heme-Induced Conformational Changes in Cytochrome c. Genceroglu MY, Cavdar C, Manioglu S, Bayraktar H. Biosensors (Basel) 13 890 (2023)
  17. Lysine carbonylation is a previously unrecognized contributor to peroxidase activation of cytochrome c by chloramine-T. Yin V, Mian SH, Konermann L. Chem Sci 10 2349-2359 (2019)
  18. Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation. González-Arzola K, Díaz-Quintana A, Bernardo-García N, Martínez-Fábregas J, Rivero-Rodríguez F, Casado-Combreras MÁ, Elena-Real CA, Velázquez-Cruz A, Gil-Caballero S, Velázquez-Campoy A, Szulc E, Gavilán MP, Ayala I, Arranz R, Ríos RM, Salvatella X, Valpuesta JM, Hermoso JA, De la Rosa MA, Díaz-Moreno I. Nat Struct Mol Biol 29 1024-1036 (2022)
  19. Phosphorylation disrupts long-distance electron transport in cytochrome c. Gomila AMJ, Pérez-Mejías G, Nin-Hill A, Guerra-Castellano A, Casas-Ferrer L, Ortiz-Tescari S, Díaz-Quintana A, Samitier J, Rovira C, De la Rosa MA, Díaz-Moreno I, Gorostiza P, Giannotti MI, Lagunas A. Nat Commun 13 7100 (2022)
  20. X-ray structure of bovine heart cytochrome c at high ionic strength. Merlino A. Biometals 31 277-284 (2018)


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