Giant mitochondria in acute lymphocytic leukemia

Eguchi, Mitsuoki; Iwama, Yoshihiko; Ochiai, Futaha; Ishikawa, Kohji; Sakakibara, Hitoshi; Sakamaki, Hisashi; Furukawa, Toshiharu

doi:10.1016/0014-4800(87)90008-6

Cited by 9 publications

(8 citation statements)

References 18 publications

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“…have been linked to diseases such as Parkinson disease [11], acute lymphocytic leukemia [12], and microvascular alterations in renal allografts [13]. Fractionating mitochondria populations by size could thus provide an important tool to assess the biomolecular differences in organelle subpopulations.…”

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confidence: 99%

Continuous organelle separation in an insulator‐based dielectrophoretic device

et al. 2022

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Heterogeneity in organelle size has been associated with devastating human maladies such as neurodegenerative diseases or cancer. Therefore, assessing the size‐based subpopulation of organelles is imperative to understand the biomolecular foundations of these diseases. Here, we demonstrated a ratchet migration mechanism using insulator‐based dielectrophoresis in conjunction with a continuous flow component that allows the size‐based separation of submicrometer particles. The ratchet mechanism was realized in a microfluidic device exhibiting an array of insulating posts, tailoring electrokinetic and dielectrophoretic transport. A numerical model was developed to elucidate the particle migration and the size‐based separation in various conditions. Experimentally, the size‐based separation of a mixture of polystyrene beads (0.28 and 0.87 μ$\umu $m) was accomplished demonstrating good agreement with the numerical model. Furthermore, the size‐based separation of mitochondria was investigated using a mitochondria mixture isolated from HepG2 cells and HepG2 cells carrying the gene Mfn‐1 knocked out, indicating distinct size‐related migration behavior. With the presented continuous flow separation device, larger amounts of fractionated organelles can be collected in the future allowing access to the biomolecular signature of mitochondria subpopulations differing in size.

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confidence: 99%

Continuous organelle separation in an insulator‐based dielectrophoretic device

et al. 2022

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“…PRC) has been evaluated in oncocytic models, which is also suggestive of the fact that decreased mitochondrial function is compensated by an increase in mitochondrial biogenesis to support the bioenergetic demands of the proliferating tumor (Gasparre et al 2013 ). With the advent of TEM, papers have reported the morphology of leukemic cells and the variation in mitochondrial morphology (Sharp et al 1979 ; Eguchi et al 1987 ). However, since a role for mitochondrial dysfunction and mitochondrial dynamics in cancer is strongly postulated, it becomes equally important to investigate the changes taking place at the cristae level to get a proper insight into the causes and consequences of mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural changes in cristae of lymphoblasts in acute lymphoblastic leukemia parallel alterations in biogenesis markers

et al. 2021

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We explored the link between mitochondrial biogenesis and mitochondrial morphology using transmission electron microscopy (TEM) in lymphoblasts of pediatric acute lymphoblastic leukemia (ALL) patients and compared these characteristics between tumors and control samples. Gene expression of mitochondrial biogenesis markers was analysed in 23 ALL patients and 18 controls and TEM for morphology analysis was done in 15 ALL patients and 9 healthy controls. The area occupied by mitochondria per cell and the cristae cross-sectional area was observed to be significantly higher in patients than in controls (p-value = 0.0468 and p-value< 0.0001, respectively). The mtDNA copy numbers, TFAM, POLG, and c-myc gene expression were significantly higher in ALL patients than controls (all p-values< 0.01). Gene Expression of PGC-1α was higher in tumor samples. The analysis of the correlation between PGC-1α expression and morphology parameters i.e., both M/C ratio and cristae cross-sectional area revealed a positive trend (r = 0.3, p = 0.1). The increased area occupied by mitochondria and increased cristae area support the occurrence of cristae remodelling in ALL. These changes might reflect alterations in cristae dynamics to support the metabolic state of the cells by forming a more condensed network. Ultrastructural imaging can be useful for affirming changes occurring at a subcellular organellar level.

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“…Previous studies have classified the various shapes of large mitochondria into two types: those that show welldeveloped cristae characterized by complicated cristae [22,25], closely packed cristae [7,25,49,54, 56], vesicular cristae [11,41], and those that show poorly-developed cristae characterized by short and peripherally-displaced cristae with unstructured matrix [33-36, 43, 51, 53, 58, 64], concentric-circled cristae [11], and sparse cristae [11]. The large mitochondria seen in the present study tended to fall under the first type.…”

Section: Discussionmentioning

confidence: 99%

“…Large mitochondria (giant mitochondria) generally appear under conditions of drug influence [6,44,45,51,57,59-61], aging [8,29,39,41,63], growth and cell cycle [7,22,[33][34][35][36]54], disease [11,12,15,25,46,47,49,52], and nutritional deficiency [9,48,50,64]. However, the purpose and function of these mitochondria remain unclear.…”

Section: Introductionmentioning

confidence: 99%