Science· 2026Q1
BAK and BAX form a multiprotein complex to drive mtDNA efflux and caspase-independent cell death
- 1citations
- Q1SCImago
- 2026year
Short summary
BAK and BAX form a novel multiprotein complex with VDAC1/2 and prohibitins that directly releases mitochondrial DNA (mtDNA) and triggers caspase-independent cell death, distinct from their role in apoptosis.
AI-generated from the title and abstract; the full text is not read.
Key points
- A macromolecular complex containing BAK, BAX, VDAC1/2, and prohibitins was purified.
- This complex releases mtDNA from mitoplasts.
- BAX-BAK activation leads to VDAC closure, calcium influx, and mtDNA efflux.
- Loss of VDAC1, VDAC2, or prohibitins prevents mtDNA efflux and caspase-independent cell death without affecting MOMP.
AI-generated from the title and abstract; the full text is not read.
Abstract
The apoptotic regulators BAX and BAK, once activated, form homo-oligomers to trigger mitochondrial outer membrane permeabilization (MOMP), activating the apoptosome and caspases. Activation of BAX-BAK without apoptosome activation triggers sustained efflux of mitochondrial DNA (mtDNA) and caspase-independent cell death. However, the molecular basis of mtDNA efflux remains unclear. We purified a macromolecular complex comprising BAK, BAX, activator BH3-only molecules, voltage-dependent anion channels 1 and 2 (VDAC1 and VDAC2), and prohibitins that released mtDNA from mitoplasts. BAX-BAK activation resulted in VDAC closure, mitochondrial calcium influx, and mtDNA efflux. Loss of VDAC1, VDAC2, or prohibitins prevented BAX-BAK activation–induced mtDNA efflux and caspase-independent cell death without affecting MOMP or mitochondrial inner membrane herniation. These findings support differential regulation of cytochrome c and mtDNA efflux by distinct BAX-BAK complexes.
The authors' abstract, as published at the source. Science, 2026 · DOI ↗
Continue with a free account
Ask the paper: 3 free questions a day about this paper; save it, get its citation, new summaries every day for your field. Takeaways are Premium.
Continue free on the webSign in with Google or Apple; no card needed. You come back to this paper.
On your phone:
Field: Molecular Biology
Molecular BiologyBiochemistry, Genetics and Molecular Biology