Limited predictive value of TFAM in mitochondrial biogenesis

Kozhukhar, Natalya; Alexeyev, Mikhail

doi:10.1016/j.mito.2019.08.001

Cited by 30 publications

(14 citation statements)

References 48 publications

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“…Contrary to our expectation, we found the opposite trend in mRNA levels of TFAM , its downstream effector. This observation was consistent with no increase in the mitochondrial DNA copy number, as TFAM is involved in mitochondrial DNA replication [ 57 ], but is not always a good marker of mitochondrial biogenesis [ 58 ]. This is also consistent with no change in the number of mitochondria.…”

Section: Discussionsupporting

confidence: 70%

Dual Effect of Combined Metformin and 2-Deoxy-D-Glucose Treatment on Mitochondrial Biogenesis and PD-L1 Expression in Triple-Negative Breast Cancer Cells

Repas

Zupin

Vodlan

et al. 2022

Cancers

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Metformin and 2-deoxy-D-glucose (2DG) exhibit multiple metabolic and immunomodulatory anti-cancer effects, such as suppressed proliferation or PD-L1 expression. Their combination or 2DG alone induce triple-negative breast cancer (TNBC) cell detachment, but their effects on mitochondria, crucial for anchorage-independent growth and metastasis formation, have not yet been evaluated. In the present study, we explored the effects of metformin, 2DG and their combination (metformin + 2DG) on TNBC cell mitochondria in vitro. Metformin + 2DG increased mitochondrial mass in TNBC cells. This was associated with an increased size but not number of morphologically normal mitochondria and driven by the induction of mitochondrial biogenesis rather than suppressed mitophagy. 2DG and metformin + 2DG strongly induced the unfolded protein response by inhibiting protein N-glycosylation. Together with adequate energy stress, this was one of the possible triggers of mitochondrial enlargement. Suppressed N-glycosylation by 2DG or metformin + 2DG also caused PD-L1 deglycosylation and reduced surface expression in MDA-MB-231 cells. PD-L1 was increased in low glucose and normalized by both drugs. 2DG and metformin + 2DG reduced PD-1 expression in Jurkat cells beyond the effects on activation, while cytokine secretion was mostly preserved. Despite increasing mitochondrial mass in TNBC cells, metformin and 2DG could therefore potentially be used as an adjunct therapy to improve anti-tumor immunity in TNBC.

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Section: Discussionsupporting

confidence: 70%

Dual Effect of Combined Metformin and 2-Deoxy-D-Glucose Treatment on Mitochondrial Biogenesis and PD-L1 Expression in Triple-Negative Breast Cancer Cells

Repas

Zupin

Vodlan

et al. 2022

Cancers

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show abstract

“…Although cancerous cells have declined mitochondria number, some extracted data present increments in the expression of TFAM, PGC-1α, and NRF1 genes [32][33][34]. However, a late report raises the uncertainty of the TFAM level's indicated as a biogenesis marker, due to its failure in accommodation to mtDNA quantity and the expression of mtDNA-encoded polypeptides [35]. The consequences of mitochondrial biogenesis comprise of boosting of mitochondrial-associated dysfunction, declining of pathologic oxidative stress, and oxidative phosphorylation efficiency.…”

Section: Mitochondrial Biogenesismentioning

confidence: 99%

Targeting Mitochondrial Biogenesis with Polyphenol Compounds

Chodari

Aytemir

Vahedi

et al. 2021

Oxidative Medicine and Cellular Longevity

105

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Appropriate mitochondrial physiology is an essential for health and survival. Cells have developed unique mechanisms to adapt to stress circumstances and changes in metabolic demands, by meditating mitochondrial function and number. In this context, sufficient mitochondrial biogenesis is necessary for efficient cell function and haemostasis, which is dependent on the regulation of ATP generation and maintenance of mitochondrial DNA (mtDNA). These procedures play a primary role in the processes of inflammation, aging, cancer, metabolic diseases, and neurodegeneration. Polyphenols have been considered as the main components of plants, fruits, and natural extracts with proven therapeutic effects during the time. These components regulate the intracellular pathways of mitochondrial biogenesis. Therefore, the current review is aimed at representing an updated review which determines the effects of different natural polyphenol compounds from various plant kingdoms on modulating signaling pathways of mitochondrial biogenesis that could be a promising alternative for the treatment of several disorders.

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“…Notably, a recent study has underlined that the relationship between TFAM expression and mitochondrial biogenesis is more complex than is generally appreciated and may be ambiguous in most mammalian cells. As TFAM does not always exhibit parallel with the mtDNA copy number, TFAM should be used judiciously as a marker of mitochondrial biogenesis ( Kozhukhar and Alexeyev, 2019 ).…”

Section: Overview Of the Mitochondrial Biogenesismentioning

confidence: 99%

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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Mitochondrial function is multifaceted in response to cellular energy homeostasis and metabolism, with the generation of adenosine triphosphate (ATP) through the oxidative phosphorylation (OXPHOS) being one of their main functions. Selective elimination of mitochondria by mitophagy, in conjunction with mitochondrial biogenesis, regulates mitochondrial function that is required to meet metabolic demand or stress response. Growth hormone (GH) binds to the GH receptor (GHR) and induces the JAK2/STAT5 pathway to activate the synthesis of insulin-like growth factor 1 (IGF1). The GH–GHR–IGF1 axis has been recognized to play significant roles in somatic growth, including cell proliferation, differentiation, division, and survival. In this review, we describe recent discoveries providing evidence for the contribution of the GH–GHR–IGF1 axis on mitochondrial biogenesis, mitophagy (or autophagy), and mitochondrial function under multiple physiological conditions. This may further improve our understanding of the effects of the GH–GHR–IGF1 axis on mitochondrial function, which may be controlled by the delicate balance between mitochondrial biogenesis and mitophagy. Specifically, we also highlight the challenges that remain in this field.

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Limited predictive value of TFAM in mitochondrial biogenesis

Cited by 30 publications

References 48 publications

Dual Effect of Combined Metformin and 2-Deoxy-D-Glucose Treatment on Mitochondrial Biogenesis and PD-L1 Expression in Triple-Negative Breast Cancer Cells

Dual Effect of Combined Metformin and 2-Deoxy-D-Glucose Treatment on Mitochondrial Biogenesis and PD-L1 Expression in Triple-Negative Breast Cancer Cells

Targeting Mitochondrial Biogenesis with Polyphenol Compounds

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

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