Journal Article

FZJ-2023-00695

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Probing the Link between Pancratistatin and Mitochondrial Apoptosis through Changes in the Membrane Dynamics on the Nanoscale

Castillo, S. R. ; Rickeard, B. W. ; DiPasquale, M. ; Nguyen, M. H. L. ; Lewis-Laurent, A. ; Doktorova, M. ; Kav, B.FZJ* ; Miettinen, M. S. ; Nagao, M. ; Kelley, E. G. ; Marquardt, D. (Corresponding author)

2022
American Chemical Society Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.molpharmaceut.1c00926

Abstract: Pancratistatin (PST) is a natural antiviral alkaloid that has demonstrated specificity toward cancerous cells and explicitly targets the mitochondria. PST initiates apoptosis while leaving healthy, noncancerous cells unscathed. However, the manner by which PST induces apoptosis remains elusive and impedes the advancement of PST as a natural anticancer therapeutic agent. Herein, we use neutron spin-echo (NSE) spectroscopy, molecular dynamics (MD) simulations, and supporting small angle scattering techniques to study PST's effect on membrane dynamics using biologically representative model membranes. Our data suggests that PST stiffens the inner mitochondrial membrane (IMM) by being preferentially associated with cardiolipin, which would lead to the relocation and release of cytochrome c. Second, PST has an ordering effect on the lipids and disrupts their distribution within the IMM, which would interfere with the maintenance and functionality of the active forms of proteins in the electron transport chain. These previously unreported findings implicate PST's effect on mitochondrial apoptosis.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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