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Nature-inspired delivery of mitochondria-targeted angiotensin receptor blocker.
Phillip, Jude M; Lin, Ran; Cheetham, Andrew; Stern, David; Li, Yukang; Wang, Yuzhu; Wang, Han; Rini, David; Cui, Honggang; Walston, Jeremy D; Abadir, Peter M.
Afiliação
  • Phillip JM; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Lin R; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Cheetham A; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Stern D; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Li Y; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Wang Y; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Wang H; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Rini D; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Cui H; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Walston JD; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Abadir PM; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
PNAS Nexus ; 1(4): pgac147, 2022 Sep.
Article em En | MEDLINE | ID: mdl-36082235
ABSTRACT
Mitochondria are critical regulators of cellular function and survival. We have previously demonstrated that functional angiotensin receptors embedded within the inner mitochondrial membrane modulate mitochondrial energy production and free radical generation. The expression of mitochondrial angiotensin II type-1 receptors increases during aging, with a complementary decrease in angiotensin II type-2 receptor density. To address this age-associated mitochondrial dysfunction, we have developed a mitochondria-targeted delivery system to effectively transport angiotensin type-1 receptor blocker-Losartan (mtLOS) into the inner mitochondrial membrane. We engineered mtLOS to become active within the mitochondria after cleavage by mitochondrial peptidases. Our data demonstrate effective and targeted delivery of mtLOS into the mitochondria, compared to a free Losartan, or Losartan conjugated to a scrambled mitochondrial target signal peptide, with significant shifts in mitochondrial membrane potential upon mtLOS treatment. Furthermore, engineered mitochondrial-targeting modalities could open new avenues to transport nonmitochondrial proteins into the mitochondria, such as other macromolecules and therapeutic agents.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article