Mitochondrial cristae narrowing upon higher 2-oxoglutarate load
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00517532" target="_blank" >RIV/67985823:_____/19:00517532 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/19:10472032
Result on the web
<a href="https://doi.org/10.1016/j.bbabio.2019.06.015" target="_blank" >https://doi.org/10.1016/j.bbabio.2019.06.015</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bbabio.2019.06.015" target="_blank" >10.1016/j.bbabio.2019.06.015</a>
Alternative languages
Result language
angličtina
Original language name
Mitochondrial cristae narrowing upon higher 2-oxoglutarate load
Original language description
Hypoxia causes mitochondrial cristae widening, enabled by the similar to 20% degradation of Mic60/mitofilin, with concomitant clustering of the MICOS complex, reflecting the widening of crista junctions (outlets) (Plecita-Hlavata et al. FASEB J., 2016 30:1941-1957). Attempting to accelerate metabolism by the addition of membrane-permeant dimethyl-2-oxoglutarate (dm2OG) to HepG2 cells pre-adapted to hypoxia, we found cristae narrowing by transmission electron microscopy. Glycolytic HepG2 cells, which downregulate hypoxic respiration, instantly increased respiration with dm2OG. Changes in intracristal space (ICS) morphology were also revealed by 3D super-resolution microscopy using Eos-conjugated ICS-located lactamase-beta. Cristae topology was resolved in detail by focused-ion beam/scanning electron microscopy (FIB/SEM). The spatial relocations of key cristae-shaping proteins were indicated by immunocytochemical stochastic 3D super-resolution microscopy (dSTORM), while analyzing inter-antibody-distance histograms: i) ATP-synthase dimers exhibited a higher fraction of shorter inter-distances between bound F-1-alpha primary Alexa-Fluor-647-conjugated antibodies, indicating cristae narrowing. ii) Mic60/mitofilin clusters (established upon hypoxia) decayed, restoring isotropic random Mic60/mitofilin distribution (a signature of normoxia). iii) outer membrane SAMM50 formed more focused clusters. Less abundant fractions of higher ATP-synthase oligomers of hypoxic samples on blue-native electrophoresis became more abundant fractions at the high dm2OG load and at normoxia. This indicates more labile ATP-synthase dimeric rows established at crista rims upon hypoxia, strengthened at normoxia or dm20G-substrate load. Hypothetically, the increased Krebs substrate load stimulates the cross-linking/strengthening of rows of ATP-synthase dimers at the crista rims, making them sharper. Crista narrowing ensures a more efficient coupling of proton pumping to ATP synthesis. We demonstrated that cristae morphology changes even within minutes.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
<a href="/en/project/LM2015062" target="_blank" >LM2015062: National Infrastructure for Biological and Medical Imaging</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochimica Et Biophysica Acta-Bioenergetics
ISSN
0005-2728
e-ISSN
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Volume of the periodical
1860
Issue of the periodical within the volume
8
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
20
Pages from-to
659-678
UT code for WoS article
000480668900007
EID of the result in the Scopus database
2-s2.0-85068374730