ArticleThe Journal of experimental medicine2001
Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein rR and Bcl-2.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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105 citing papers in PubMed, 267 citations in OpenAlex.
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- Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments.Circulation research · 2024Review
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- Conformational change of adenine nucleotide translocase-1 mediates cisplatin resistance induced by EBV-LMP1.EMBO molecular medicine · 2021Article
- Endoplasmic reticulum & mitochondrial calcium homeostasis: The interplay with viruses.Mitochondrion · 2021Article
- Animal Coronaviruses Induced Apoptosis.Life (Basel, Switzerland) · 2021Review
- Mitocanic Di- and Triterpenoid Rhodamine B Conjugates.Molecules (Basel, Switzerland) · 2020Review
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- Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019Review
- Simultaneous Multiparameter Cellular Energy Metabolism Profiling of Small Populations of Cells.Scientific reports · 2018Article
- Evaluation of antiretroviral effect on mitochondrial DNA depletion among HIV-infected patients in Bali.HIV/AIDS (Auckland, N.Z.) · 2018Article
- Adipose Tissue in HIV Infection.Comprehensive Physiology · 2017Review
- The immunoregulatory role of alpha enolase in dendritic cell function during Chlamydia infection.BMC immunology · 2017Article
- The HIV-1 Vpr Protein: A Multifaceted Target for Therapeutic Intervention.International journal of molecular sciences · 2017Review
45 more citing papers are in PubMed but not listed here.
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20 authors at 7 institutions in 2 countries.
Funding
Abstract
Viral protein R (Vpr), an apoptogenic accessory protein encoded by HIV-1, induces mitochondrial membrane permeabilization (MMP) via a specific interaction with the permeability transition pore complex, which comprises the voltage-dependent anion channel (VDAC) in the outer membrane (OM) and the adenine nucleotide translocator (ANT) in the inner membrane. Here, we demonstrate that a synthetic Vpr-derived peptide (Vpr52-96) specifically binds to the intermembrane face of the ANT with an affinity in the nanomolar range. Taking advantage of this specific interaction, we determined the role of ANT in the control of MMP. In planar lipid bilayers, Vpr52-96 and purified ANT cooperatively form large conductance channels. This cooperative channel formation relies on a direct protein-protein interaction since it is abolished by the addition of a peptide corresponding to the Vpr binding site of ANT. When added to isolated mitochondria, Vpr52-96 uncouples the respiratory chain and induces a rapid inner MMP to protons and NADH. This inner MMP precedes outer MMP to cytochrome c. Vpr52-96-induced matrix swelling and inner MMP both are prevented by preincubation of purified mitochondria with recombinant Bcl-2 protein. In contrast to König's polyanion (PA10), a specific inhibitor of the VDAC, Bcl-2 fails to prevent Vpr52-96 from crossing the mitochondrial OM. Rather, Bcl-2 reduces the ANT-Vpr interaction, as determined by affinity purification and plasmon resonance studies. Concomitantly, Bcl-2 suppresses channel formation by the ANT-Vpr complex in synthetic membranes. In conclusion, both Vpr and Bcl-2 modulate MMP through a direct interaction with ANT.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.