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Full text
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Author(s):
Show less - |
Ferreira, Julio C. B.
[1, 2]
;
Campos, Juliane C.
[2]
;
Qvit, Nir
[1]
;
Qi, Xin
[1, 3]
;
Bozi, Luiz H. M.
[2]
;
Bechara, Luiz R. G.
[2]
;
Lima, Vanessa M.
[2]
;
Queliconi, Bruno B.
[4]
;
Disatnik, Marie-Helene
[1]
;
Dourado, Paulo M. M.
[5]
;
Kowaltowski, Alicia J.
[4]
;
Mochly-Rosen, Daria
[1]
Total Authors: 12
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| Affiliation: | [1] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 - USA
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo, SP - Brazil
[3] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 - USA
[4] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Inst Heart, BR-05403010 Sao Paulo, SP - Brazil
Total Affiliations: 5
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| Document type: |
Journal article
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| Source: |
NATURE COMMUNICATIONS;
v. 10,
JAN 18 2019.
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| Web of Science Citations: |
4
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| Abstract |
We previously demonstrated that beta II protein kinase C (beta IIPKC) activity is elevated in failing hearts and contributes to this pathology. Here we report that beta IIPKC accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria in heart failure. beta IIPKC siRNA or a beta IIPKC inhibitor mitigates mitochondrial fragmentation and cell death. We confirm that Mfn1-beta IIPKC interaction alone is critical in inhibiting mitochondrial function and cardiac myocyte viability using SAM beta A, a rationally-designed peptide that selectively antagonizes Mfn1-ss IIPKC association. SAM beta A treatment protects cultured neonatal and adult cardiac myocytes, but not Mfn1 knockout cells, from stress-induced death. Importantly, SAM beta A treatment re-establishes mitochondrial morphology and function and improves cardiac contractility in rats with heart failure, suggesting that SAM beta A may be a potential treatment for patients with heart failure. (AU) |
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| FAPESP's process: |
10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism
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| Grantee: | Alicia Juliana Kowaltowski |
| Support type: |
Research Projects - Thematic Grants
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| FAPESP's process: |
16/09611-0 - Doxorubicin-induced cardiotoxicity: role of mitochondrial retrograde signaling activated by protein imbalance
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| Grantee: | Luiz Henrique Marchesi Bozi |
| Support type: |
Scholarships in Brazil - Post-Doctorate
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| FAPESP's process: |
12/05765-2 - Contribution of aldehyde dehydrogenase 2 to heart failure development
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| Grantee: | Julio Cesar Batista Ferreira |
| Support type: |
Research Grants - Young Investigators Grants
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| FAPESP's process: |
15/20783-5 - Protein quality control in dysfunctional/atrophic skeletal muscle: role of b2-adrenoceptor
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| Grantee: | Julio Cesar Batista Ferreira |
| Support type: |
Regular Research Grants
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| FAPESP's process: |
17/16540-5 - EXERCISE, LIFESPAN AND HEALTHSPAN: A MOLECULAR AND LONGITUDINAL APPROACH TO STUDY THEIR INTERACTIONS
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| Grantee: | Juliane Cruz Campos |
| Support type: |
Scholarships in Brazil - Post-Doctorate
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| FAPESP's process: |
10/00028-4 - Characterization of mitochondrial fusion and fission in heart failure: effects of exercise training
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| Grantee: | Patricia Chakur Brum |
| Support type: |
Regular Research Grants
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| FAPESP's process: |
17/16694-2 - Impact of 4-hydroxinonenal on DICER regulation: a translational approach
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| Grantee: | Julio Cesar Batista Ferreira |
| Support type: |
Regular Research Grants
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| FAPESP's process: |
17/11142-1 - Mitochondrial formyl peptides as signaling molecules: new perspective in the treatment of cardiac ischemia/reperfusion injury.
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| Grantee: | Luiz Roberto Grassmann Bechara |
| Support type: |
Scholarships in Brazil - Post-Doctorate
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| FAPESP's process: |
15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment
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| Grantee: | Carlos Eduardo Negrão |
| Support type: |
Research Projects - Thematic Grants
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| FAPESP's process: |
09/12349-2 - Characterization of mitochondrial function and dynamics in cardiac dysfunction-induced myocardial infarction in rats
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| Grantee: | Juliane Cruz Campos |
| Support type: |
Scholarships in Brazil - Master
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| FAPESP's process: |
16/01633-5 - BETA2-ADRENOCEPTOR ACTIVATION COUNTERACTS SKELETAL MUSCLE WEAKNESS/WASTING: ROLE OF AUTOPHAGY
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| Grantee: | Juliane Cruz Campos |
| Support type: |
Scholarships abroad - Research Internship - Doctorate
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