Abstract
Mitochondria can be incorporated into mammalian cells by simple co-incubation of isolated mitochondria with cells, without the need of transfection reagents or any other type of intervention. This phenomenon was termed mitochondrial transformation, and although it was discovered in 1982, currently little is known regarding its mechanism(s). Here we demonstrate that mitochondria can be transformed into recipient cells very quickly, and co-localize with endogenous mitochondria. The isolated mitochondria interact directly with cells, which engulf the mitochondria with cellular extensions in a way, which may suggest the involvement of macropinocytosis or macropinocytosis-like mechanisms in mitochondrial transformation. Indeed, macropinocytosis inhibitors but not clathrin-mediated endocytosis inhibition-treatments, blocks mitochondria transformation. The integrity of the mitochondrial outer membrane and its proteins is essential for the transformation of the mitochondria into cells; cells can distinguish mitochondria from similar particles and transform only intact mitochondria. Mitochondrial transformation is blocked in the presence of the heparan sulfate molecules pentosan polysulfate and heparin, which indicate crucial involvement of cellular heparan sulfate proteoglycans in the mitochondrial transformation process.
Highlights
Mitochondria can be incorporated into mammalian cells by simple co-incubation of isolated mitochondria with cells, without the need of transfection reagents or any other type of intervention
Transmission electron microscopy (TEM) revealed that the isolated mitochondria interact directly with the recipient cells, which engulf the mitochondria with cellular extensions that might suggest mitochondrial transformation occurs via macropinocytosis
Our results show that the isolated mitochondria were transformed into the HepG2 cells (Fig. 1A,B), MCF7 cells and HEK 293 cells (Fig. S2), and that transformation persisted for at least 6 days in HepG2 cells following 24 h incubation (Figs 1B1 and 2)
Summary
Mitochondria can be incorporated into mammalian cells by simple co-incubation of isolated mitochondria with cells, without the need of transfection reagents or any other type of intervention This phenomenon was termed mitochondrial transformation, and it was discovered in 1982, currently little is known regarding its mechanism(s). Numerous diseases and disorders are associated with mitochondrial dysfunctions and mutations, including metabolic pathologies[9,10,11,12,13] and neurodegenerative diseases[14,15,16] It was first reported three decades ago, in 1982, that isolated mitochondria can be incorporated in vitro into cells by a simple co-incubation of isolated mitochondria with cells, without the need for transfection reagents, supplements to the medium or any other type of intervention[17]. We show that pentosan polysulfate and heparin, both heparan sulfated www.nature.com/scientificreports/
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
