Massive endocytosis triggered by surface membrane palmitoylation under mitochondrial control in BHK fibroblasts

Donald W. Hilgmann, Michael Fine, Maurine E. Linder, Benjamin C. Jennings, Mei Jung Lin

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Large Ca transients cause massive endocytosis (MEND) in BHK fibroblasts by nonclassical mechanisms. We present evidence that MEND depends on mitochondrial permeability transition pore (PTP) openings, followed by coenzyme A (CoA) release, acyl CoA synthesis, and membrane protein palmitoylation. MEND is blocked by inhibiting mitochondrial Ca uptake or PTP openings, depleting fatty acids, blocking acyl CoA synthesis, metabolizing CoA, or inhibiting palmitoylation. It is triggered by depolarizing mitochondria or promoting PTP openings. After mitochondrial MEND blockade, MEND is restored by cytoplasmic acyl CoA or CoA. MEND is blocked by siRNA knockdown of the plasmalemmal acyl transferase, DHHC5. When acyl CoA is abundant, transient H2O2 oxidative stress or PKC activation initiates MEND, but the immediate presence of H2O2 prevents MEND. The PTP inhibitor, NIM811, significantly increases plasmalemma in normally growing cells. Thus, the MEND pathway may contribute to constitutive as well as pathological plasmalemma turnover in dependence on mitochondrial stress signaling.

Original languageEnglish (US)
Article numbere01293
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Nov 26 2013

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Lipoylation
Acyl Coenzyme A
Fibroblasts
Endocytosis
Coenzyme A
Membranes
Mitochondria
Oxidative stress
Permeability
Transferases
Small Interfering RNA
Membrane Proteins
Fatty Acids
Chemical activation
Oxidative Stress

ASJC Scopus subject areas

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

Cite this

Massive endocytosis triggered by surface membrane palmitoylation under mitochondrial control in BHK fibroblasts. / Hilgmann, Donald W.; Fine, Michael; Linder, Maurine E.; Jennings, Benjamin C.; Lin, Mei Jung.

In: eLife, Vol. 2013, No. 2, e01293, 26.11.2013.

Research output: Contribution to journalArticle

Hilgmann, Donald W. ; Fine, Michael ; Linder, Maurine E. ; Jennings, Benjamin C. ; Lin, Mei Jung. / Massive endocytosis triggered by surface membrane palmitoylation under mitochondrial control in BHK fibroblasts. In: eLife. 2013 ; Vol. 2013, No. 2.
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