Megamitochondria Initiate Differentiation of Monolayer Cells into Detached Dome Cells That Proliferate by a Schizogony-Like Amitotic Process

Mitonucleon-initiated dome formation involves structural changes occurring over a 20 to 24 hour period in monolayer cells induced by a serum factor. The earliest observable change is the fusion of monolayer cells into a syncytium in which nuclei aggregate and become surrounded by a membrane that stains for endogenous biotin. Each of these structures is further surrounded by a fraction of the mitochondria that arise in the syncytium following initiation of dome formation. The mitochondria fuse around the chromatin aggregate in a structure we have called a mitonucleon. Within mitonucleons, a gaseous vacuole is generated that can be seen in protrusions of the apical membrane pressuring chromatin into a pyknotic state. Eventually that pressure, together with whatever enzymatic changes have occurred in the bolus of chromatin, results in DNA fragmentation. The fragments drawn out through the syncytium by a unipolar spindle are arrayed in a configuration that appears open both to epigenetic changes and to DNA repair and replication by polyteny. The fragmented DNA stretched across the syncytial space, hardly detectable by light microscopy, becomes visible approximately half way through the differentiation as the filaments thicken in what looks like replication by polyteny. This “recycling” of attached monolayer cells into detached dome cells must include DNA replication since the number of cells in the resulting domes is greater than the number of monolayer cells by 30% or more. The resulting DNA associates into a mass of chromatin which will “segment” into polyploid structures and then into what appear to be diploid nuclei over a period of 2 to 4 hours. When the layer of nuclei has filled the syncytium, the nuclei are cellularized, forming dome cells rising up from the monolayer and arching over a fluid cavity. Dome cells can extend into gland-like structures by the same mitonucleon dependent amitotic process observed in dome formation. Some of the characteristics of this process resemble the amitotic process of schizogony among single-celled eukaryotic parasites of the apicomplexan phylum. Mitonucleon initiated amitotic proliferation results in synthesis of dozens of dome cell nuclei in a period of 20 to 24 hours, so it is much more efficient than mitosis. Cells generated by this process and their progeny would also not be sensitive to agents that inhibit mitosis suggesting that the process, as an alternative to mitosis, might be activated in cancers that become resistant to some cytotoxic drugs.

Pediatric non-alcoholic steatohepatitis:The first report on the ultrastructure of hepatocyte mitochondria

AIM: To investigate the ultrastructure of abnormal hepatocyte mitochondria, including their cellular and hepatic zonal distribution, in bioptates in pediatric non-alcoholic steatohepatitis (NASH).

Opaque Polyploid Cells in Ishikawa Endometrial Cultures Are Capable of Forming Megamitochondria, Organelles Derived from the Adaptation of Fused Mitochondria Whose Capacity to Develop Gaseous Vacuoles Suggests CO₂Retention and Hypoxic Metabolism

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.