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Ferreira 2019 Nat Commun

From Bioblast
Publications in the MiPMap
Ferreira JCB, Campos JC, Qvit N, Qi X, Bozi LHM, Bechara LRG, Lima VM, Queliconi BB, Disatnik MH, Dourado PMM, Kowaltowski AJ, Mochly-Rosen D (2019) A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats. Nat Commun 10:329.

» PMID: 30659190 Open Access

Ferreira JCB, Campos JC, Qvit N, Qi X, Bozi LHM, Bechara LRG, Lima VM, Queliconi BB, Disatnik MH, Dourado PMM, Kowaltowski AJ, Mochly-Rosen D (2019) Nat Commun

Abstract: We previously demonstrated that beta II protein kinase C (βIIPKC) activity is elevated in failing hearts and contributes to this pathology. Here we report that βIIPKC 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. βIIPKC siRNA or a βIIPKC inhibitor mitigates mitochondrial fragmentation and cell death. We confirm that Mfn1-βIIPKC interaction alone is critical in inhibiting mitochondrial function and cardiac myocyte viability using SAMβA, a rationally-designed peptide that selectively antagonizes Mfn1-βIIPKC association. SAMβA treatment protects cultured neonatal and adult cardiac myocytes, but not Mfn1 knockout cells, from stress-induced death. Importantly, SAMβA treatment re-establishes mitochondrial morphology and function and improves cardiac contractility in rats with heart failure, suggesting that SAMβA may be a potential treatment for patients with heart failure.

Bioblast editor: Plangger M O2k-Network Lab: BR Sao Paulo Ferreira JCB, BR Sao Paulo Kowaltowski AJ


Labels: MiParea: Respiration  Pathology: Cardiovascular 

Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: NS  HRR: Oxygraph-2k 

2019-01