Berridge Michael V, Neuzil Jiri
Malaghan Institute of Medical Research, Wellington, New Zealand.
School of Medical Science, Griffith University, Southport, Australia.
Clin Exp Pharmacol Physiol. 2017 Dec;44 Suppl 1:15-20. doi: 10.1111/1440-1681.12764. Epub 2017 Sep 20.
The view that genes are constrained within somatic cells is challenged by in vitro evidence, and more recently by in vivo studies which demonstrate that mitochondria with their mitochondrial DNA (mtDNA) payload not only can, but do move between cells in tumour models and in mouse models of tissue damage. Using mouse tumour cell models without mtDNA to reflect mtDNA damage, we have shown that these cells grow tumours only after acquiring mtDNA from cells in the local microenvironment resulting in respiration recovery, tumorigenesis and metastasis. Mitochondrial transfer between cells has also been demonstrated following ischaemia-induced injury in the heart and brain and in lung epithelium, and following lung inflammation. In vitro investigations suggest that stem cells may be mitochondrial donors. The ability of mitochondria to move between cells appears to be an evolutionarily-conserved phenomenon, relevant to diseases with compromised mitochondrial function including neurodegenerative, neuromuscular and cardiovascular diseases as well as cancer and ageing.
基因局限于体细胞内的观点受到了体外证据的挑战，最近体内研究也对其提出了质疑，这些研究表明携带线粒体DNA（mtDNA）的线粒体不仅能够，而且确实会在肿瘤模型和组织损伤小鼠模型的细胞之间移动。利用不含mtDNA的小鼠肿瘤细胞模型来反映mtDNA损伤，我们已经表明，这些细胞只有在从局部微环境中的细胞获取mtDNA后才能生长肿瘤，从而导致呼吸恢复、肿瘤发生和转移。在心脏、大脑和肺上皮的缺血性损伤后以及肺部炎症后，也证实了细胞间的线粒体转移。体外研究表明干细胞可能是线粒体的供体。线粒体在细胞间移动的能力似乎是一种进化上保守的现象，与线粒体功能受损的疾病有关，包括神经退行性疾病、神经肌肉疾病和心血管疾病以及癌症和衰老。
