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Abstract
Opaque polyploid cells capable of forming megamitochondria are a constant feature in colonies of Ishikawa endometrial epithelia, accounting for approximately 5% - 10% of the cells. Opaque cells appear to communicate with other opaque cells via membrane extensions and with other cells in a colony by extra-cellular vesicles. Opaque cells form first as rectangular structures, somewhat larger than surrounding monolayer cells. The cells eventually round up, remaining in the colony for 20 or more hours before detaching. The most unusual characteristic of Ishikawa opaque cells is their capacity to form mitonucleons, megamitochondria that surround aggregated chromatin. This paper reviews evidence that adaptations resulting in megamitochondria include a loss of the capacity for oxidative phosphorylation leaving the adapted megamitochondria reliant on metabolism such as reductive carboxylation.
Highlights
Mitonucleons form at the center of such cells, staining brightly for endogenous biotin as seen in the light micrographs in Figure 1 and Figure 2
Three or four mitonucleons form within a syncytium, fill with gas, and elevate separately so that, for a short period of time, they create multiple protuberances in an “expanding” syncytial apical membrane that most likely includes endoplasmic reticulum membranes associated with the giant mitochondria, an association observed in tissues such as endometrium [37], in the adrenal cortex [38] and in human hepatocytes [25]
Can we assume similar functions for megamitochondria in higher organisms? Do megamitochondria within opaque giant cells achieve localized hypoxia by virtue of an adapted membrane structure fortified with cholesterol? The observation that megamitochondria retain gases even as evidence of their capacity for oxidative phosphorylation dramatically decreases [52], together with the observations of a reciprocal relationship between membrane permeability to CO2 and O2 uptake [61], suggests that adapted mitochondria may be mostly hypoxic
Summary
Dr Jinsong Liu’s laboratory [1] has been studying a cell type called polyploid giant cells (PGCC) found in ovarian as well as in other cancer cell lines [2] [3]. Dr Liu and colleagues characterized PGCC’s whose formation was stimulated by CoCl2, demonstrating that the giant cells express cancer stem cell markers together with markers characteristic of normal cells. Spheroids derived from single PGCCs can grow into a wide spectrum of human neoplasms, including germ cell tumors, high-grade and low-grade carcinomas and benign tissues leading these researchers to suggest that PGCC’s are cancer stem cells and the somatic equivalents of blastomeres
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