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Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
Published on: March 23, 2015
Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release
Seong-Woon Yu1, Yingfei Wang, Didrik S Frydenlund
1double daggerCentre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, POB 1105, Blindern, N-0317, Oslo, Norway.
ASN Neuro
|October 30, 2009
Summary
A second pool of apoptosis-inducing factor (AIF) exists in brain mitochondria, located on the outer membrane. This pool rapidly causes neuronal death during parthanatos, offering therapeutic potential for neurological disorders.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Poly(ADP-ribose) polymerase-1-dependent cell death (parthanatos) is crucial in neurological conditions like ischemia/reperfusion injury and excitotoxicity.
- Previous research indicated uncleaved apoptosis-inducing factor (AIF) release during parthanatos, suggesting an uncharacterized mitochondrial AIF pool.
Purpose of the Study:
- To identify and characterize a novel pool of AIF in brain mitochondria.
- To investigate the role of this AIF pool in parthanatos-induced neuronal death.
Main Methods:
- Multiple biochemical analyses to detect AIF localization.
- Immunogold electron microscopy in mouse brain.
- NMDA (N-methyl-d-aspartate) treatment to induce parthanatos.
Main Results:
- A previously unknown AIF pool was identified, with approximately 30% loosely associated with the outer mitochondrial membrane.
- Immunogold electron microscopy confirmed AIF localization on both outer and inner mitochondrial membranes in vivo.
- About 20% of uncleaved AIF rapidly translocated to the nucleus, causing neuronal death upon NMDA treatment.
Conclusions:
- This study reveals a second, readily releasable pool of AIF in brain mitochondria, located on the outer membrane.
- This outer mitochondrial AIF pool does not require cleavage and is sufficient to induce cell death during parthanatos.
- Targeting this outer mitochondrial AIF pool presents a promising therapeutic strategy for neurological disorders involving parthanatos.
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