Mitochondria in stem cells

Lonergan, Thomas A.; Bavister, Barry D.; Brenner, Carol A.

doi:10.1016/j.mito.2007.05.002

Cited by 130 publications

(111 citation statements)

References 60 publications

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“…Interestingly, steadystate expression of POLG has been found to be essential for the maintenance of pluripotency in mouse ESCs [28]. Since the whole process of active replication of mtDNA is regulated by nuclear encoded factors [44,52], it is tempting to speculate that genetic reprogramming, which resets the nuclei to an embryonic-like epigenetic state, might also relay information to the mitochondria, reverting them to an analogous immature state. Indeed, inhibition of p53 signaling not only increases the efficiency of iPSC generation [16,17] but also regulates mitochondrial biogenesis and causes mtDNA depletion [53][54].…”

Section: Repression Of the Mitochondrial/oxidative Stress Pathway In mentioning

confidence: 99%

The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells

et al. 2010

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The ability of stem cells to propagate indefinitely is believed to occur via the fine modulation of pathways commonly involved in cellular senescence, including the telomerase, the p53, and the mitochondrial/oxidative stress pathways. Induced pluripotent stem cells (iPSCs) are a novel stem cell population obtained from somatic cells through forced expression of a set of genes normally expressed in embryonic stem cells (ESCs). These reprogrammed cells acquire self-renewal properties and appear almost undistinguishable from ESCs in terms of morphology, gene expression, and differentiation potential. Accordingly, iPSCs exhibit alterations of the senescence-related telomerase and p53 signaling pathways. However, although treatments with antioxidants have been recently shown to enhance cellular reprogramming, detailed information regarding the state of the mitochondrial/oxidative stress pathway in iPSCs is still lacking. Mitochondria undergo specific changes during organismal development and aging. Thus, addressing whether somatic mitochondria within iPSCs acquire ESC-like features or retain the phenotype of the parental cell is an unanswered but relevant question. Herein, we demonstrate that somatic mitochondria within human iPSCs revert to an immature ESC-like state with respect to organelle morphology and distribution, expression of nuclear factors involved in mitochondrial biogenesis, content of mitochondrial DNA, intracellular ATP level, oxidative damage, and lactate generation. Upon differentiation, mitochondria within iPSCs and ESCs exhibited analogous maturation and anaerobic-to-aerobic metabolic modifications. Overall, the data highlight that human iPSCs and ESCs, although not identical, share similar mitochondrial properties and suggest that cellular reprogramming can modulate the mitochondrial/oxidative stress pathway, thus inducing a rejuvenated state capable of escaping cellular senescence.

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Section: Repression Of the Mitochondrial/oxidative Stress Pathway In mentioning

confidence: 99%

The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells

et al. 2010

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“…Reduced ATP level may limit the energy supply for the oocytes or preimplantation embryos (Thouas et al, 2004) and high ATP content may support high Δφ m effectively . However, embryos are contained in the hypoxic uterine lumen, which is not beneficial for ATP synthesis (Lonergan et al, 2007). So high ATP level can also limit embryo development.…”

Section: Mitochondrial Polarity Atp Content and Oocyte Agingmentioning

confidence: 99%

Mitochondrial functions on oocytes and preimplantation embryos

Wang

Zou

et al. 2009

J. Zhejiang Univ. Sci. B

134

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Oocyte quality has long been considered as a main limiting factor for in vitro fertilization (IVF). In the past decade, extensive observations demonstrated that the mitochondrion plays a vital role in the oocyte cytoplasm, for it can provide adenosine triphosphate (ATP) for fertilization and preimplantation embryo development and also act as stores of intracellular calcium and proapoptotic factors. During the oocyte maturation, mitochondria are characterized by distinct changes of their distribution pattern from being homogeneous to heterogeneous, which is correlated with the cumulus apoptosis. Oocyte quality decreases with the increasing maternal age. Recent studies have shown that low quality oocytes have some age-related dysfunctions, which include the decrease in mitochondrial membrane potential, increase of mitochondrial DNA (mtDNA) damages, chromosomal aneuploidies, the incidence of apoptosis, and changes in mitochondrial gene expression. All these dysfunctions may cause a high level of developmental retardation and arrest of preimplantation embryos. It has been suggested that these mitochondrial changes may arise from excessive reactive oxygen species (ROS) that is closely associated with the oxidative energy production or calcium overload, which may trigger permeability transition pore opening and subsequent apoptosis. Therefore, mitochondria can be seen as signs for oocyte quality evaluation, and it is possible that the oocyte quality can be improved by enhancing the physical function of mitochondria. Here we reviewed recent advances in mitochondrial functions on oocytes.

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“…There is a parallelism in the metabolic fate directed by PPARA activation in ES cells and early embryos. ES cells are derived from ICM cells that are known to rely on oxidation of glucose to lactate for energy (Lonergan et al 2007). The early embryonic cells generate their ATP from of monocarboxylate oxidation.…”

Section: Metabolic Stress In Embryosmentioning

confidence: 99%

Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-α (PPARA) cause peroxisome proliferation in preimplantation mouse embryos

Jansen

Cashman²,

Thompson³

et al. 2009

Reproduction

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Ex vivo two-cell mouse embryos deprived of glucose in vitro can develop to blastocysts by increasing their pyruvate consumption; however, zygotes when glucose-deprived cannot adapt this metabolic profile and degenerate as morulae. Prior to their death, these glucose-deprived morulae exhibit upregulation of the H C -monocarboxylate co-transporter SLC16A7 and catalase, which partly co-localize in peroxisomes. SLC16A7 has been linked to redox shuttling for peroxisomal b-oxidation. Peroxisomal function is unclear during preimplantation development, but as a peroxisomal transporter in embryos, SLC16A7 may be involved and influenced by peroxisome proliferators such as peroxisome proliferator-activated receptor-a (PPARA). PCR confirmed Ppara mRNA expression in mouse embryos. Zygotes were cultured with or without glucose and with the PPARA-selective agonist WY14643 and the developing embryos assessed for expression of PPARA and phospho-PPARA in relation to the upregulation of SLC16A7 and catalase driven by glucose deprivation, indicative of peroxisomal proliferation. Reactive oxygen species (ROS) production and relationship to PPARA expression were also analysed. In glucose-deprived zygotes, ROS was elevated within 2 h, as were PPARA expression within 8 h and catalase and SLC16A7 after 12-24 h compared with glucose-supplied embryos. Inhibition of ROS production prevented this induction of PPARA and SLC16A7. Selective PPARA agonism with WY14643 also induced SLC16A7 and catalase expression in the presence of glucose. These data suggest that glucose-deprived cleavage stage embryos, although supplied with sufficient monocarboxylate-derived energy, undergo oxidative stress and exhibit elevated ROS, which in turn upregulates PPARA, catalase and SLC16A7 in a classical peroxisomal proliferation response.

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Mitochondria in stem cells

Cited by 130 publications

References 60 publications

The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells

The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells

Mitochondrial functions on oocytes and preimplantation embryos

Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-α (PPARA) cause peroxisome proliferation in preimplantation mouse embryos

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