Kathiresan, Meena, Martins Jr, Dorival and English, Ann M. 
ORCID: https://orcid.org/0000-0002-3696-7710
(2014)
Respiration triggers heme transfer from cytochrome c
peroxidase to catalase in yeast mitochondria.
Proceedings of the National Academy of Sciences of the United States of America (PNAS) ISSN 1091-6490, 111
(49).
pp. 17468-17473.
ISSN 0027-8424 ESSN: 1091-6490
Preview |
Text (Publisher's Version) (application/pdf)
1MB14.respiration.pdf - Published Version Available under License Spectrum Terms of Access. |
Preview |
Text (Supplemental Material) (application/pdf)
1MB14.respiration.sapp.pdf - Supplemental Material Available under License Spectrum Terms of Access. |
Official URL: https://doi.org/10.1073/pnas.1409692111
Abstract
In exponentially growing yeast, the heme enzyme, cytochrome c peroxidase (Ccp1) is targeted to the mitochondrial intermembrane space. When the fermentable source (glucose) is depleted, cells switch to respiration and mitochondrial H2O2 levels rise. It has long been assumed that CCP activity detoxifies mitochondrial H2O2 because of the efficiency of this activity in vitro. However, we find that a large pool of Ccp1 exits the mitochondria of respiring cells. We detect no extramitochondrial CCP activity because Ccp1 crosses the outer mitochondrial membrane as the heme-free protein. In parallel with apoCcp1 export, cells exhibit increased activity of catalase A (Cta1), the mitochondrial and peroxisomal catalase isoform in yeast. This identifies Cta1 as a likely recipient of Ccp1 heme, which is supported by low Cta1 activity in ccp1Δ cells and the accumulation of holoCcp1 in cta1Δ mitochondria. We hypothesized that Ccp1’s heme is labilized by hyperoxidation of the protein during the burst in H2O2 production as cells begin to respire. To test this hypothesis, recombinant Ccp1 was hyperoxidized with excess H2O2 in vitro, which accelerated heme transfer to apomyoglobin added as a surrogate heme acceptor. Furthermore, the proximal heme Fe ligand, His175, was found to be ∼85% oxidized to oxo-histidine in extramitochondrial Ccp1 isolated from 7-d cells, indicating that heme labilization results from oxidation of this ligand. We conclude that Ccp1 responds to respiration-derived H2O2 via a previously unidentified mechanism involving H2O2-activated heme transfer to apoCta1. Subsequently, the catalase activity of Cta1, not CCP activity, contributes to mitochondrial H2O2 detoxification.
| Divisions: | Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry |
|---|---|
| Item Type: | Article |
| Refereed: | Yes |
| Authors: | Kathiresan, Meena and Martins Jr, Dorival and English, Ann M. |
| Journal or Publication: | Proceedings of the National Academy of Sciences of the United States of America (PNAS) ISSN 1091-6490 |
| Date: | 9 December 2014 |
| Digital Object Identifier (DOI): | 10.1073/pnas.1409692111 |
| ID Code: | 985132 |
| Deposited By: | MIA MASSICOTTE |
| Deposited On: | 28 May 2019 15:22 |
| Last Modified: | 29 May 2019 12:46 |
| Additional Information: | "This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. 1073/pnas.1409692111/-/DCSupplemental." |
References:
1. Kaput J, Goltz S, Blobel G (1982) Nucleotide sequence of the yeast nuclear gene for cytochrome c peroxidase precursor. Functional implications of the pre sequence for protein transport into mitochondria. J Biol Chem 257(24):15054–15058.2. Suppanz IE, Wurm CA, Wenzel D, Jakobs S (2009) The m-AAA protease processes cytochrome c peroxidase preferentially at the inner boundary membrane of mitochondria. Mol Biol Cell 20(2):572–580.
3. Michaelis G, et al. (2005) Mitochondrial signal peptidases of yeast: The rhomboid peptidase Pcp1 and its substrate cytochrome C peroxidase. Gene 354:58–63.
4. Sels AA, Cocriamont C (1968) Induced conversion of a protein precursor into cytochrome C peroxidase during adaptation of yeast to oxygen. Biochem Biophys Res Commun 32(2):192–198.
5. Djavadi-Ohaniance L, Rudin Y, Schatz G (1978) Identification of enzymically inactive apocytochrome c peroxidase in anaerobically grown Saccharomyces cerevisiae. J Biol Chem 253(12):4402–4407.
6. Volkov AN, Nicholls P, Worrall JAR (2011) The complex of cytochrome c and cytochrome c peroxidase: The end of the road? Biochim Biophys Acta 1807(11):1482 1503.
7. Perrone GG, Tan S-X, Dawes IW (2008) Reactive oxygen species and yeast apoptosis. Biochim Biophys Acta 1783(7):1354–1368.
8. Kwon M, Chong S, Han S, Kim K (2003) Oxidative stresses elevate the expression of cytochrome c peroxidase in Saccharomyces cerevisiae. Biochim Biophys Acta 1623(1):1–5.
9. Jiang H, English AM (2006) Phenotypic analysis of the ccp1Delta and ccp1Deltaccp1W191F mutant strains of Saccharomyces cerevisiae indicates that cytochrome c peroxidase functions in oxidative-stress signaling. J Inorg Biochem 100(12):1996–2008.
10. Martins D, Kathiresan M, English AM (2013) Cytochrome c peroxidase is a mitochondrial heme-based H2O2 sensor that modulates antioxidant defense. Free Radic Biol Med 65:541–551.
11. Martins D, Titorenko VI, English AM (2014) Cells with impaired mitochondrial H2O2 sensing generate less •OH radicals and live longer. Antioxid Redox Signal 21(10): 1490–1503.
12. Skulachev VP (1998) Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett 423(3):275–280.
13. Cohen G, Rapatz W, Ruis H (1988) Sequence of the Saccharomyces cerevisiae CTA1 gene and amino acid sequence of catalase A derived from it. Eur J Biochem 176(1): 159–163.
14. Hartig A, Ruis H (1986) Nucleotide sequence of the Saccharomyces cerevisiae CTT1 gene and deduced amino-acid sequence of yeast catalase T. Eur J Biochem 160(3): 487–490.
15. Petrova VY, Drescher D, Kujumdzieva AV, Schmitt MJ (2004) Dual targeting of yeast catalase A to peroxisomes and mitochondria. Biochem J 380(Pt 2):393–400.
16. Zimniak P, Hartter E, Woloszczuk W, Ruis H (1976) Catalase biosynthesis in yeast: Formation of catalase A and catalase T during oxygen adaptation of Saccharomyces cerevisiae. Eur J Biochem 71(2):393–398.
17. Kaput J, Brandriss MC, Prussak-Wieckowska T (1989) In vitro import of cytochrome c peroxidase into the intermembrane space: Release of the processed form by intact mitochondria. J Cell Biol 109(1):101–112.
18. Yaffe MP (2003) The cutting edge of mitochondrial fusion. Nat Cell Biol 5(6):497–499.
19. Dingwall C, Laskey RA (1986) Protein import into the cell nucleus. Annu Rev Cell Biol 2:367–390.
20. Whelan SP, Zuckerbraun BS (2013) Mitochondrial signaling: Forwards, backwards, and in between. Oxid Med Cell Longev 2013:351613.
21. Feissner R, Xiang Y, Kranz RG (2003) Chemiluminescent-based methods to detect subpicomole levels of c-type cytochromes. Anal Biochem 315(1):90–94.
22. Mesquita A, et al. (2010) Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H2O2 and superoxide dismutase activity. Proc Natl Acad Sci USA 107(34):15123–15128.
23. Goldberg AA, et al. (2009) Effect of calorie restriction on the metabolic history of chronologically aging yeast. Exp Gerontol 44(9):555–571.
24. Burke PV, Raitt DC, Allen LA, Kellogg EA, Poyton RO (1997) Effects of oxygen concentration on the expression of cytochrome c and cytochrome c oxidase genes in yeast. J Biol Chem 272(23):14705–14712.
25. Wright RM, Poyton RO (1990) Release of two Saccharomyces cerevisiae cytochrome genes, COX6 and CYC1, from glucose repression requires the SNF1 and SSN6 gene products. Mol Cell Biol 10(3):1297–1300.
26. Erman JE, Yonetani T (1975) A kinetic study of the endogenous reduction of the oxidized sites in the primary cytochrome c peroxidase-hydrogen peroxide compound. Biochim Biophys Acta 393(2):350–357.
27. Paul J, Chen W, Ohlsson P-I, Smith M (1998) Heme transfer reactions: An important prerequisite for synthetic oxygen carriers. Turkish J Chem 22(2):103–108.
28. Hargrove MS, et al. (1994) Stability of myoglobin: A model for the folding of heme proteins. Biochemistry 33(39):11767–11775.
29. Adams PA (1977) The kinetics of the recombination reaction between apomyoglobin and alkaline haematin. Biochem J 163(1):153–158.
30. Fox T, Tsaprailis G, English AM (1994) Fluorescence investigation of yeast cytochrome c peroxidase oxidation by H2O2 and enzyme activities of the oxidized enzyme. Biochemistry 33(1):186–191.
31. Tsaprailis G, English AM (2003) Different pathways of radical translocation in yeast cytochrome c peroxidase and its W191F mutant on reaction with H(2)O(2) suggest an antioxidant role. J Biol Inorg Chem 8(3):248–255.
32. Yogev O, Naamati A, Pines O (2011) Fumarase: A paradigm of dual targeting and dual localized functions. FEBS J 278(22):4230–4242.
33. Tsaprailis G, Chan DW, English AM (1998) Conformational states in denaturants of cytochrome c and horseradish peroxidases examined by fluorescence and circular dichroism. Biochemistry 37(7):2004–2016.
34. Dumont ME, Cardillo TS, Hayes MK, Sherman F (1991) Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae. Mol Cell Biol 11(11):5487–5496.
35. Fisher WR, Taniuchi H, Anfinsen CB (1973) On the role of heme in the formation of the structure of cytochrome c. J Biol Chem 248(9):3188–3195.
36. Hörtner H, et al. (1982) Regulation of synthesis of catalases and iso-1-cytochrome c in Saccharomyces cerevisiae by glucose, oxygen and heme. Eur J Biochem 128(1): 179–184.
37. Woloszczuk W, Sprinson DB, Ruis H (1980) The relation of heme to catalase apoprotein synthesis in yeast. J Biol Chem 255(6):2624–2627.
38. Uchida K, Kawakishi S (1994) Identification of oxidized histidine generated at the active site of Cu,Zn-superoxide dismutase exposed to H2O2. Selective generation of 2-oxo-histidine at the histidine 118. J Biol Chem 269(4):2405–2410.
39. Traoré DAK, et al. (2009) Structural and functional characterization of 2-oxo-histidine in oxidized PerR protein. Nat Chem Biol 5(1):53–59.
40. Lee J-W, Helmann JD (2006) The PerR transcription factor senses H2O2 by metalcatalysed histidine oxidation. Nature 440(7082):363–367.
41. Goodrich LE, Paulat F, Praneeth VKK, Lehnert N (2010) Electronic structure of hemenitrosyls and its significance for nitric oxide reactivity, sensing, transport, and toxicity in biological systems. Inorg Chem 49(14):6293–6316.
42. He C, Neya S, Knipp M (2011) Breaking the proximal Fe(II)-N(His) bond in heme proteins through local structural tension: Lessons from the heme b proteins nitrophorin 4, nitrophorin 7, and related site-directed mutant proteins. Biochemistry 50(40):8559–8575.
43. Ristow M, Zarse K (2010) How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis). Exp Gerontol 45(6):410–418.
44. Decker BL, Wickner WT (2006) Enolase activates homotypic vacuole fusion and protein transport to the vacuole in yeast. J Biol Chem 281(20):14523–14528.
45. Charizanis C, Juhnke H, Krems B, Entian KD (1999) The mitochondrial cytochrome c peroxidase Ccp1 of Saccharomyces cerevisiae is involved in conveying an oxidative stress signal to the transcription factor Pos9 (Skn7). Mol Gen Genet 262(3):437–447.
46. Martins D, English AM (2014) Catalase activity is stimulated by H(2)O(2) in rich culture medium and is required for H(2)O(2) resistance and adaptation in yeast. Redox Biol 2: 308–313.
47. Lee J, et al. (1999) Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. J Biol Chem 274(23):16040–16046.
48. Toledano MB, Delaunay A, Monceau L, Tacnet F (2004) Microbial H2O2 sensors as archetypical redox signaling modules. Trends Biochem Sci 29(7):351–357.
49. Kiley PJ, Storz G (2004) Exploiting thiol modifications. PLoS Biol 2(11):e400.
50. Erman JE, Vitello LB (2002) Yeast cytochrome c peroxidase: Mechanistic studies via protein engineering. Biochim Biophys Acta 1597(2):193–220.
51. Chen S, Brockenbrough JS, Dove JE, Aris JP (1997) Homocitrate synthase is located in the nucleus in the yeast Saccharomyces cerevisiae. J Biol Chem 272(16):10839–10846.
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.
Repository Staff Only: item control page
Download Statistics
Download Statistics