Enriched endoplasmic reticulum-mitochondria interactions result in mitochondrial dysfunction and apoptosis in oocytes from obese mice

Zhao, Lihong; Lu, Tengfei; Gao, Lei; Fu, Xiangwei; Zhu, Shi-En; Hou, Yunpeng

doi:10.1186/s40104-017-0195-z

Cited by 52 publications

(44 citation statements)

References 27 publications

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“…Thus, it provides the possibility that some IMC proteins also localize in MAMs during spermatogenesis, especially the mitochondrial outer membrane proteins, such as TDRKH, which might serve as a mitochondrial scaffold to recruit piRNA pathway factors [62]. Interestingly, mammalian oocytes also contain MAM structure [103,104], but no reports demonstrate that female germ cells have IMC and CB-like structures during oogenesis. Yet, the functions and underlying mechanism of MAM formation in both male and female germ cells are still elusive to date.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Wang

Guo

et al. 2020

Cells

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Multiple specific granular structures are present in the cytoplasm of germ cells, termed nuage, which are electron-dense, non-membranous, close to mitochondria and/or nuclei, variant size yielding to different compartments harboring different components, including intermitochondrial cement (IMC), piP-body, and chromatoid body (CB). Since mitochondria exhibit different morphology and topographical arrangements to accommodate specific needs during spermatogenesis, the distribution of mitochondria-associated nuage is also dynamic. The most relevant nuage structure with mitochondria is IMC, also called pi-body, present in prospermatogonia, spermatogonia, and spermatocytes. IMC is primarily enriched with various Piwi-interacting RNA (piRNA) proteins and mainly functions as piRNA biogenesis, transposon silencing, mRNA translation, and mitochondria fusion. Importantly, our previous work reported that mitochondria-associated ER membranes (MAMs) are abundant in spermatogenic cells and contain many crucial proteins associated with the piRNA pathway. Provocatively, IMC functionally communicates with other nuage structures, such as piP-body, to perform its complex functions in spermatogenesis. Although little is known about the formation of both IMC and MAMs, its distinctive characters have attracted considerable attention. Here, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We discuss the roles of the structural components in spermatogenesis and piRNA biogenesis, which provide new insights into mitochondria-associated germinal structures in germ cell development and male reproduction. Cells 2020, 9, 399 2 of 20Mitochondria-associated ER membranes (MAMs) are tight structural contacts, also named as MERCs (mitochondria-ER contacts);~20% of the mitochondrial surface are jointly opposing and contact directly with the ER, yielding to approximately 10 and 30 nm in distance [4,5]. MAMs participate in several cellular signaling pathways, including calcium transmission, phospholipid exchange, intracellular trafficking, autophagy, ER stress, mitochondrial biogenesis, and inflammasome formation. Disturbances to MAMs lead to neurodegenerative diseases and cancer [6,7]. Our previous work reported that MAMs are abundant in both human and mouse spermatogenic cells, and contain many crucial proteins that are associated with the Piwi-interacting RNA (piRNA) pathway [8]. However, the functions of MAMs are still mysterious in spermatogenesis.In this review, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We summarize the ultra-structure of IMC and MAMs in mouse spermatocyte, as shown in Figure 1A. We also discuss the roles of the structural components in piRNA biogenesis and propose that further s...

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Section: Discussionmentioning

confidence: 99%

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Wang

Guo

et al. 2020

Cells

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“…Under these conditions, Pacs2 deficiency improves glucose tolerance and increases hepatic insulin signaling . In oocytes from obese mice, genetic repression of Pacs2 decreases Ca 2+ influx into mitochondria and ROS production . In Pacs2 knockout mice, liver expression of FGF21 is increased and mice are resistant to diet‐induced obesity (Fig B).…”

Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 96%

“…An increase in mitochondria–ER contacts, increased expression of IP3R1, IP3R2, and PACS2 protein levels, and greater mitochondrial Ca 2+ uptake and apoptosis has been documented in oocytes from HFD‐treated mice . These changes compromise oocyte maturation.…”

Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 99%

Metabolic implications of organelle–mitochondria communication

2019

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Cellular organelles are not static but show dynamism—a property that is likely relevant for their function. In addition, they interact with other organelles in a highly dynamic manner. In this review, we analyze the proteins involved in the interaction between mitochondria and other cellular organelles, especially the endoplasmic reticulum, lipid droplets, and lysosomes. Recent results indicate that, on one hand, metabolic alterations perturb the interaction between mitochondria and other organelles, and, on the other hand, that deficiency in proteins involved in the tethering between mitochondria and the ER or in specific functions of the interaction leads to metabolic alterations in a variety of tissues. The interaction between organelles is an emerging field that will permit to identify key proteins, to delineate novel modulation pathways, and to elucidate their implications in human disease.

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“…By contrast, treatment with U73122 increased the rate of oocyte maturation and increased the level of apoptosis, in line with the revised activation protocol, where both calcium ionophore and SrCl 2 /cytochalasin B can promote the quality of ovine somatic cell nuclear transfer embryos in terms of total cell number, apoptosis, and ploidy . However, this was inconsistent with the finding that increased levels of mitochondrial Ca 2+ caused by enriched mitochondria‐associated endoplasmic reticulum membranes was associated with impaired cytoplasmic maturation and increased apoptosis in oocytes from obese mice . PKC inhibitors can induce apoptosis in Xenopus laevis oocytes, which is in agreement with our findings that U73122 inhibits PKC and increases apoptosis in porcine oocytes.…”

Section: Discussionmentioning

confidence: 90%

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro

Chen

Cheng

Yang

et al. 2020

J of Cellular Biochemistry

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Oocyte apoptosis can be used as an indicator of oocyte quality and development competency. Phospholipase C (PLC) is a critical enzyme that participates in phosphoinositide metabolic regulation and performs many functions, including the regulation of reproduction. In this study, we aimed to explore whether PLC participates in the regulation of apoptosis in porcine oocytes and investigated its possible mechanism. In porcine oocytes, 0.5 μM U73122 (the PLC inhibitor) was considered to be the best concentration to facilitate maturation, and 0.5 μM m-3M3FBS (the PLC activator) was regarded as the most appropriate concentration to inhibit maturation. The percentage of cleavage and blastocysts treated with 0.5 μM U73122 was lower than that of the control group. Furthermore, the percentage of cleavage and blastocysts treated with 0.5 μM m-3M3FBS was higher than that of the control group. The relative PLC messenger RNA (mRNA) expression tested by a quantitative real-time polymerase chain reaction was found to be inhibited by 0.5 μM U73122 or activated by 0.5 μM m-3M3FBS. The relative mRNA abundance of BAK, BAX, CASP3, CASP8, and TP53 and protein abundance of Bak, cleaved caspase-3, caspase-8, and P53 was activated by U73122 or inhibited by m-3M3FBS, while the relative mRNA and protein level of BCL6 showed the opposite trend. The intracellular Ca 2+ concentration increased and the expression of PLCB1 protein also increased in porcine oocytes when they were cultured with 0.5 μM m-3M3FBS for 44 hours. The abundance of proteins PKCβ and CAMKIIα and the expression of several downstream genes (CDC42, NFATc1, NFATc2, NFκB, and NLK) were activated by m-3M3FBS or inhibited by U73122. Our findings indicate that PLC inhibits apoptosis and maturation in porcine oocytes. The intracellular Ca 2+ concentration, two Ca 2+ -sensitive proteins, and several downstream genes were positively regulated by PLC. K E Y W O R D Sapoptosis, Ca 2+ -sensitive proteins, intracellular Ca 2+ concentration, oocytes, phospholipase C, porcine

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Enriched endoplasmic reticulum-mitochondria interactions result in mitochondrial dysfunction and apoptosis in oocytes from obese mice

Cited by 52 publications

References 27 publications

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Metabolic implications of organelle–mitochondria communication

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro

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