INTERCELLULAR MITOCHONDRIAL TRANSFER THROUGH NANOTUBULES IS PROMOTED BY CYCLIC AMP (cAMP) IN RAT ASTROCYTES AND HUMAN GLIOBLASTOMA CELLS

KATIA E. HELFENBERGER; YANINA BENZO; ALEJANDRA DUARTE; FEDERICO FUENTES; JUAN JOSÉ PODEROSO; PAULA MALOBERTI; CECILIA PODEROSO

Mar del Plata

Congreso; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

SAIC

Nanotubules (Tunneling nanotubules, TnTs) are cell membrane projections made of F-actin fibers of nanometric diameter (up to 1 μm),which enable cytoplasmatic connections between cells. It has beenshown that mitochondria, other organelles, and cellular componentsare transferred by TnTs in several normal and tumor cell lines. TnTsestablishment has been extensively described in nervous systemcells, as neurons and astrocytes. Published evidence indicates theexistence of mitochondrial transfer through TnTs between differentcell types, such as normal and tumoral cells. Mitochondrial passagefrom normal to tumor cells restores oxidative metabolism, decreasing tumorigenic potential. A similar effect has been observed withcAMP, a very well-known astrocytes stellation promoter, which mediates mitochondrial biogenesis and tumor growth inhibition. Mitochondrial transfer within TnTs in nervous system cells have not beendemonstrated so far. Then, our goal was to analyze mitochondrialtrafficking through TnTs in normal and tumoral astrocytes and apossible effect of cAMP. We used normal rat astrocytes and humanglioblastoma U87 cells. Mitochondria and actin were probed with amito-targeted green fluorescent protein and phalloidin, respectively. Astrocytes and U87 were incubated with or without 8Br-cAMP(cAMP analogue). We analyzed images by confocal microscopy andmeasured the width of actin connections between cells. We analyzedeach culture separately; astrocytes and U87 establish thick projections containing mitochondria but treatment with cAMP promotes anincrease of TnTs-like connections with mitochondria inside (controlvs cAMP: astrocytes: 2.07±0.71 vs 0.85±0.21 μm, ***p