| Full text | |
| 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
|
| 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
|
| Document type: | Journal article |
| Source: | NATURE COMMUNICATIONS; v. 10, JAN 18 2019. |
| Web of Science Citations: | 4 |
| 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) | |
| FAPESP's process: | 10/00028-4 - Characterization of mitochondrial fusion and fission in heart failure: effects of exercise training |
| Grantee: | Patricia Chakur Brum |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment |
| Grantee: | Carlos Eduardo Negrão |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/16694-2 - Impact of 4-hydroxinonenal on DICER regulation: a translational approach |
| Grantee: | Julio Cesar Batista Ferreira |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/11142-1 - Mitochondrial formyl peptides as signaling molecules: new perspective in the treatment of cardiac ischemia/reperfusion injury. |
| Grantee: | Luiz Roberto Grassmann Bechara |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 12/05765-2 - Contribution of aldehyde dehydrogenase 2 to heart failure development |
| Grantee: | Julio Cesar Batista Ferreira |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism |
| Grantee: | Alicia Juliana Kowaltowski |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/16540-5 - Exercise, lifespan and healthspan: a molecular and longitudinal approach to study their interactions |
| Grantee: | Juliane Cruz Campos |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 09/12349-2 - Characterization of mitochondrial function and dynamics in cardiac dysfunction-induced myocardial infarction in rats |
| Grantee: | Juliane Cruz Campos |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 16/01633-5 - BETA2-ADRENOCEPTOR ACTIVATION COUNTERACTS SKELETAL MUSCLE WEAKNESS/WASTING: ROLE OF AUTOPHAGY |
| Grantee: | Juliane Cruz Campos |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 16/09611-0 - Doxorubicin-induced cardiotoxicity: role of mitochondrial retrograde signaling activated by protein imbalance |
| Grantee: | Luiz Henrique Marchesi Bozi |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 15/20783-5 - Protein quality control in dysfunctional/atrophic skeletal muscle: role of b2-adrenoceptor |
| Grantee: | Julio Cesar Batista Ferreira |
| Support Opportunities: | Regular Research Grants |