RT info:eu-repo/semantics/article
T1 Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges
A1 Lavorato, Manuela
A1 Iyer, V. Ramesh
A1 Dewight, Williams
A1 Cupo, Ryan R.
A1 Debattisti, Valentina
A1 Gomez, Ludovic
A1 Fuente Pérez, Sergio De La
A1 Zhao, Yan-Ting
A1 Valdivia, Héctor H.
A1 Hajnóczky, György
A1 Franzini-Armstrong, Clara
AB Exchanges of matrix contents are essential to the maintenance of mitochondria. Cardiac mitochondrial exchange matrix content in two ways: by direct contact with neighboring mitochondria and over longer distances. The latter mode is supported by thin tubular protrusions, called nanotunnels, that contact other mitochondria at relatively long distances. Here, we report that cardiac myocytes of heterozygous mice carrying a catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutation (A4860G) show a unique and unusual mitochondrial response: a significantly increased frequency of nanotunnel extensions. The mutation induces Ca2+ imbalance by depressing RyR2 channel activity during excitation-contraction coupling, resulting in random bursts of Ca2+ release probably due to Ca2+ overload in the sarcoplasmic reticulum. We took advantage of the increased nanotunnel frequency in RyR2A4860G+/- cardiomyocytes to investigate and accurately define the ultrastructure of these mitochondrial extensions and to reconstruct the overall 3D distribution of nanotunnels using electron tomography. Additionally, to define the effects of communication via nanotunnels, we evaluated the intermitochondrial exchanges of matrix-targeted soluble fluorescent proteins, mtDsRed and photoactivable mtPA-GFP, in isolated cardiomyocytes by confocal microscopy. A direct comparison between exchanges occurring at short and long distances directly demonstrates that communication via nanotunnels is slower.
SN 0027-8424
YR 2017
FD 2017
LK https://uvadoc.uva.es/handle/10324/70092
UL https://uvadoc.uva.es/handle/10324/70092
LA spa
NO Lavorato M, Iyer VR, Dewight W, Cupo RR, Debattisti V, Gomez L, De la Fuente S, Zhao YT, Valdivia HH, Hajnóczky G, Franzini-Armstrong C. Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E849-E858. doi: 10.1073/pnas.1617788113. Epub 2017 Jan 17. PMID: 28096415; PMCID: PMC5293110.
NO Producción Científica
DS UVaDOC
RD 23-dic-2024