Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic cardiac muscle

Mei Jung Lin, Michael Fine, Jui Yun Lu, Sandra L. Hofmann, Gary Frazier, Donald W. Hilgemann

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

In fibroblasts, large Ca transients activate massive endocytosis (MEND) that involves membrane protein palmitoylation subsequent to mitochondrial permeability transition pore (PTP) openings. Here, we characterize this pathway in cardiac muscle. Myocytes with increased expression of the acyl transferase, DHHC5, have decreased Na/K pump activity. In DHHC5-deficient myocytes, Na/K pump activity and surface area/volume ratios are increased, the palmitoylated regulatory protein, phospholemman (PLM), and the cardiac Na/Ca exchanger (NCX1) show greater surface membrane localization, and MEND is inhibited in four protocols. Both electrical and optical methods demonstrate that PTP-dependent MEND occurs during reoxygenation of anoxic hearts. Post-anoxia MEND is ablated in DHHC5-deficient hearts, inhibited by cyclosporine A (CsA) and adenosine, promoted by staurosporine (STS), reduced in hearts lacking PLM, and correlates with impaired post-anoxia contractile function. Thus, the MEND pathway appears to be deleterious in severe oxidative stress but may constitutively contribute to cardiac sarcolemma turnover in dependence on metabolic stress.

Original languageEnglish (US)
Article numbere01295
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Nov 26 2013

Fingerprint

Lipoylation
Endocytosis
Muscle
Myocardium
Pumps
Oxidative stress
Staurosporine
Muscle Cells
Fibroblasts
Transferases
Adenosine
Cyclosporine
Membrane Proteins
Sarcolemma
Physiological Stress
Membranes
Permeability
Oxidative Stress
Proteins
phospholemman

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic cardiac muscle. / Lin, Mei Jung; Fine, Michael; Lu, Jui Yun; Hofmann, Sandra L.; Frazier, Gary; Hilgemann, Donald W.

In: eLife, Vol. 2013, No. 2, e01295, 26.11.2013.

Research output: Contribution to journalArticle

Lin, Mei Jung ; Fine, Michael ; Lu, Jui Yun ; Hofmann, Sandra L. ; Frazier, Gary ; Hilgemann, Donald W. / Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic cardiac muscle. In: eLife. 2013 ; Vol. 2013, No. 2.
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