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@ARTICLE{Hofstadter:614102,
author = {Hofstadter, William A. and Cook, Katelyn C. and
Tsopurashvili, Elene and Gebauer, Robert and Pražák,
Vojtěch and Machala, Emily A. and Park, Ji Woo and
Grünewald, Kay and Quemin, Emmanuelle R. J. and Cristea,
Ileana M.},
title = {{I}nfection-induced peripheral mitochondria fission drives
{ER} encapsulations and inter-mitochondria contacts that
rescue bioenergetics},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {PUBDB-2024-05736},
pages = {7352},
year = {2024},
abstract = {The dynamic regulation of mitochondria shape via fission
and fusion is critical for cellular responses to stimuli. In
homeostatic cells, two modes of mitochondrial fission,
midzone and peripheral, provide a decision fork between
either proliferation or clearance of mitochondria. However,
the relationship between specific mitochondria shapes and
functions remains unclear in many biological contexts. While
commonly associated with decreased bioenergetics, fragmented
mitochondria paradoxically exhibit elevated respiration in
several disease states, including infection with the
prevalent pathogen human cytomegalovirus (HCMV) and
metastatic melanoma. Here, incorporating super-resolution
microscopy with mass spectrometry and metabolic assays, we
use HCMV infection to establish a molecular mechanism for
maintaining respiration within a fragmented mitochondria
population. We establish that HCMV induces fragmentation
through peripheral mitochondrial fission coupled with
suppression of mitochondria fusion. Unlike uninfected cells,
the progeny of peripheral fission enter mitochondria-ER
encapsulations (MENCs) where they are protected from
degradation and bioenergetically stabilized during
infection. MENCs also stabilize pro-viral inter-mitochondria
contacts (IMCs), which electrochemically link mitochondria
and promote respiration. Demonstrating a broader relevance,
we show that the fragmented mitochondria within metastatic
melanoma cells also form MENCs. Our findings establish a
mechanism where mitochondria fragmentation can promote
increased respiration, a feature relevant in the context of
human diseases.},
cin = {CSSB-LIV-KG},
ddc = {500},
cid = {I:(DE-H253)CSSB-LIV-KG-20220525},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39187492},
UT = {WOS:001298967100004},
doi = {10.1038/s41467-024-51680-4},
url = {https://bib-pubdb1.desy.de/record/614102},
}