Studies of the Effect of Chloramphenicol, Ethidium Bromide and Camptothecin on the Reproduction of Rous Sarcoma virus in Infected Chick Embryo Cells

Leblond-Larouche, Lorraine; Morais, Réjean; Zollinger, Max

doi:10.1099/0022-1317-44-2-323

Cited by 22 publications

(9 citation statements)

References 26 publications

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“…Poliovirus inhibits oxphos (24) and converts almost all cellular organelles except mitochondria into viral replication sites (4). Ethidium bromide treatment of Rous sarcoma virus-infected cells impaired mitochondrial functions, but not virus production or viral RNA synthesis (27). In striking contrast to most other virus infections, RV infection has a positive effect on cellular metabolism.…”

Section: Discussionmentioning

confidence: 89%

Involvement of p32 and Microtubules in Alteration of Mitochondrial Functions by Rubella Virus

Claus

Chey

Sticht

et al. 2011

J Virol

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The interaction of the rubella virus (RV) capsid (C) protein and the mitochondrial p32 protein is believed to participate in virus replication. In this study, the physiological significance of the association of RV with mitochondria was investigated by silencing p32 through RNA interference. It was demonstrated that downregulation of p32 interferes with microtubule-directed redistribution of mitochondria in RV-infected cells. However, the association of the viral C protein with mitochondria was not affected. When cell lines either pretreated with respiratory chain inhibitors or cultivated under (mild) hypoxic conditions were infected with RV, viral replication was reduced in a time-dependent fashion. Additionally, RV infection induces increased activity of mitochondrial electron transport chain complex III, which was associated with an increase in the mitochondrial membrane potential. These effects are outstanding among the examples of mitochondrial alterations caused by viruses. In contrast to the preferential localization of p32 to the mitochondrial matrix in most cell lines, RV-permissive cell lines were characterized by an almost exclusive membrane association of p32. Conceivably, this contributes to p32 function(s) during RV replication. The data presented suggest that p32 fulfills an essential function for RV replication in directing trafficking of mitochondria near sites of viral replication to meet the energy demands of the virus.Rubella virus (RV), a single-stranded RNA virus, is the sole member of the genus Rubivirus in the family Togaviridae and causes a generally mild exanthematous childhood disease. However, severe malformations known as congenital rubella syndrome may result from the infection of seronegative women, especially during the first trimester of pregnancy. The mechanisms contributing to RV teratogenesis remain largely unknown. The 5Ј-proximal open reading frame (ORF) of the genome encodes the two replicase proteins P150 and P90, while the 3Ј ORF encodes the structural proteins, the capsid (C) protein and two envelope glycoproteins (E1 and E2). Viral RNA synthesis occurs on replication complexes, which are membrane bound to a structure called the cytopathic vacuole (CPV). CPVs are of endolysosomal origin and surrounded by rough endoplasmic reticulum (RER) cisternae, the Golgi apparatus, and mitochondria (13,14). CPVs are replication factories and provide a protected environment for virus replication and assembly.The C protein of RV represents one of the few RNA virusencoded structural proteins that interact with mitochondria and is so far the only known viral protein that impairs protein transport into mitochondria (17). Additionally, the C protein participates in viral RNA synthesis (42), which is emphasized by its accumulation around CPVs (14). The C protein is also involved in the process of mitochondrial redistribution to a perinuclear region in proximity to CPVs (3,28) and interacts with the p32 protein (3). Besides its predominant localization to the matrix of mitochondria, p32 is a...

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Section: Discussionmentioning

confidence: 89%

Involvement of p32 and Microtubules in Alteration of Mitochondrial Functions by Rubella Virus

Claus

Chey

Sticht

et al. 2011

J Virol

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“…First, mitochondria play a key role in the induction of apoptosis (for review see Loeffler & Kroemer 2000). In addition, several studies have established that inhibition of mitochondrial activity, either by deleting mt-DNA (Rho 0 cells) or by blocking translation in the organelle, stops or decreases proliferation of different cell lines (Leblond-Larouche et al 1979, Morais et al 1980, Van den Bogert et al 1992. Furthermore, the general activity of the organelle, not restricted to energy production, is implicated in such regulation (Grégoire et al 1984, Buchet & Godinot 1998.…”

Section: Physiological Importance Of the Direct Mitochondrial T3 Pathwaymentioning

confidence: 99%

Thyroid hormone action in mitochondria

Wrutniak‐Cabello¹,

Casas²,

Cabello³

2001

Journal of Molecular Endocrinology

275

175

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Triiodothyronine (T3) is considered a major regulator of mitochondrial activity. In this review, we show evidence of the existence of a direct T3 mitochondrial pathway, and try to clarify the respective importance of the nuclear and mitochondrial pathways for organelle activity. Numerous studies have reported short-term and delayed T3 stimulation of mitochondrial oxygen consumption. Convincing data indicate that an early influence occurs through an extra-nuclear mechanism insensitive to inhibitors of protein synthesis. Although it has been shown that diiodothyronines could actually be T3 mediators of this short-term influence, the detection of specific T3-binding sites, probably corresponding to a 28 kDa c-Erb A 1 protein of the inner membrane, also supports a direct T3 influence. The more delayed influence of thyroid hormone upon mitochondrial respiration probably results from mechanisms elicited at the nuclear level, including changes in phospholipid turnover and stimulation of uncoupling protein expression, leading to an increased inner membrane proton leak. However, the involvement of a direct mitochondrial T3 pathway leading to a rapid stimulation of mitochondrial protein synthesis has to be considered.Both pathways are obviously involved in the T3 stimulation of mitochondrial genome transcription. First, a 43 kDa c-Erb A 1 protein located in the mitochondrial matrix (p43), acting as a potent T3-dependent transcription factor of the mitochondrial genome, induces early stimulation of organelle transcription. In addition, T3 increases mitochondrial TFA expression, a mitochondrial transcription factor encoded by a nuclear gene. Similarly, the stimulation of mitochondriogenesis by thyroid hormone probably involves both pathways. In particular, the c-erb A gene simultaneously encodes a nuclear and a mitochondrial T3 receptor (p43), thus ensuring coordination of the expression of the mitochondrial genome and of nuclear genes encoding mitochondrial proteins.Recent studies concerning the physiological importance of the direct mitochondrial T3 pathway involving p43 led to the conclusion that it is not only involved in the regulation of fuel metabolism, but also in the regulation of cell differentiation. As the processes leading to or resulting from differentiation are energy-consuming, p43 coordination of metabolism and differentiation could be of significant importance in the regulation of development.

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“…In particular, mitochondrial events are involved in the preliminary steps of apoptosis (1), and inhibition of mitochondrial activity, either by deleting mtDNA (rho°cells) or by blocking translation in the organelle, has been shown to stop or decrease the proliferation of different cell lines (2)(3)(4). Furthermore, the general activity of the organelle, not restricted to energy production, is implicated in such regulation (5,6).…”

mentioning

confidence: 99%

Mitochondrial Activity Is Involved in the Regulation of Myoblast Differentiation through Myogenin Expression and Activity of Myogenic Factors

Rochard¹,

Rodier²,

Casas³

et al. 2000

Journal of Biological Chemistry

187

163

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To characterize the regulatory pathways involved in the inhibition of cell differentiation induced by the impairment of mitochondrial activity, we investigated the relationships occurring between organelle activity and myogenesis using an avian myoblast cell line (QM7). The inhibition of mitochondrial translation by chloramphenicol led to a potent block of myoblast differentiation. Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone and oligomycin, which affect the organelle at different levels, exerted a similar influence. In addition, we provided evidence that this phenomenon was not the result of an alteration in cell viability. Conversely, overexpression of the mitochondrial T3 receptor (p43) stimulated organelle activity and strongly potentiated myoblast differentiation. The involvement of mitochondrial activity in an actual regulation of myogenesis is further supported by results demonstrating that the muscle regulatory gene myogenin, in contrast to CMD1 (chicken MyoD) and myf5, is a specific transcriptional target of mitochondrial activity. Whereas myogenin mRNA and protein levels were down-regulated by chloramphenicol treatment, they were up-regulated by p43 overexpression, in a positive relationship with the expression level of the transgene. We also found that myogenin or CMD1 overexpression in chloramphenicol-treated myoblasts did not restore differentiation, thus indicating that an alteration in mitochondrial activity interferes with the ability of myogenic factors to induce terminal differentiation.Recent studies emphasize that mitochondria, in addition to their well known involvement in the regulation of energy metabolism, are implicated in the regulation of cell growth and differentiation. In particular, mitochondrial events are involved in the preliminary steps of apoptosis (1), and inhibition of mitochondrial activity, either by deleting mtDNA (rho°cells) or by blocking translation in the organelle, has been shown to stop or decrease the proliferation of different cell lines (2-4). Furthermore, the general activity of the organelle, not restricted to energy production, is implicated in such regulation (5, 6). In addition, mitochondrial protein synthesis inhibition is associated with the impairment of differentiation of different cell lines, such as mouse erythroleukemia (7) and mastocytoma cells (8), neurons (9), and human (10), avian (11) or murine myoblasts (12). In agreement with these data, several pathologies are associated with mitochondrial disorders, even if the links between mitochondrial genome rearrangements or activity and pathological symptoms are not always clearly established. Despite these reports, little is known about the molecular mechanisms involved in these regulations. First, the exclusive use of inhibitors of mitochondrial function in previous reports was not fully adapted to demonstrating the occurrence of an actual regulatory pathway involving mitochondrial activity in the regulation of cell differentiation. Second, the nature of the molecular signals underlying the...

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Studies of the Effect of Chloramphenicol, Ethidium Bromide and Camptothecin on the Reproduction of Rous Sarcoma virus in Infected Chick Embryo Cells

Cited by 22 publications

References 26 publications

Involvement of p32 and Microtubules in Alteration of Mitochondrial Functions by Rubella Virus

Involvement of p32 and Microtubules in Alteration of Mitochondrial Functions by Rubella Virus

Thyroid hormone action in mitochondria

Mitochondrial Activity Is Involved in the Regulation of Myoblast Differentiation through Myogenin Expression and Activity of Myogenic Factors

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