Distribution and Apoptotic Function of Outer Membrane Proteins Depend on Mitochondrial Fusion

David Weaver, Verónica Eisner, Xingguo Liu, P. Várnai, L. Hunyady, Atan Gross, György Hajnóczky

Research output: Contribution to journalArticle

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Abstract

Cells deficient in mitochondrial fusion have been shown to have defects linked to the exchange of inner membrane and matrix components. Because outer-mitochondrial membrane (OMM) constituents insert directly from the cytoplasm, a role for fusion in theirintermitochondrial transfer was unanticipated. Here,we show that fibroblasts lacking the GTPases responsible for OMM fusion, mitofusins 1 and 2 (MFN1 and MFN2), display more heterogeneous distribution of OMM proteins. Proteins with different modes of OMM association display varying degrees of heterogeneity in Mfn1/2-/- cells and different kinetics of transfer during fusion in fusion-competent cells. Proapoptotic Bak exhibits marked heterogeneity, which is normalized upon expression of MFN2. Bak is critical for Bid-induced OMM permeabilization and cytochrome c release, and Mfn1/2-/- cells show dysregulation of Bid-dependent apoptotic signaling. Bid sensitivity of Bak-deficient mitochondria is regained upon fusion with Bak-containing mitochondria. Thus, OMM protein distribution depends on mitochondrial fusion and is a locus of apoptotic dysfunction in conditions of fusion deficiency.

Original languageEnglish
Pages (from-to)870-878
Number of pages9
JournalMolecular Cell
Volume54
Issue number5
DOIs
Publication statusPublished - Jun 5 2014

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Mitochondrial Dynamics
Mitochondrial Membranes
Membrane Proteins
Mitochondrial Proteins
Mitochondria
Membrane Fusion
Cell Fusion
GTP Phosphohydrolases
Cytochromes c
Cytoplasm
Fibroblasts
Membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Distribution and Apoptotic Function of Outer Membrane Proteins Depend on Mitochondrial Fusion. / Weaver, David; Eisner, Verónica; Liu, Xingguo; Várnai, P.; Hunyady, L.; Gross, Atan; Hajnóczky, György.

In: Molecular Cell, Vol. 54, No. 5, 05.06.2014, p. 870-878.

Research output: Contribution to journalArticle

Weaver, David ; Eisner, Verónica ; Liu, Xingguo ; Várnai, P. ; Hunyady, L. ; Gross, Atan ; Hajnóczky, György. / Distribution and Apoptotic Function of Outer Membrane Proteins Depend on Mitochondrial Fusion. In: Molecular Cell. 2014 ; Vol. 54, No. 5. pp. 870-878.
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