Structure, mechanism, and regulation of mitochondrial DNA transcription initiation

Basu, Urmimala; Bostwick, Alicia M.; Das, Kalyan; Dittenhafer‐Reed, Kristin E.; Patel, Smita S.

doi:10.1074/jbc.rev120.011202

Cited by 72 publications

(49 citation statements)

References 226 publications

(349 reference statements)

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“…Mitochondrial DNA (mtDNA) is packaged with specific proteins in compact DNA–protein complexes named mitochondrial nucleoids (mt-nucleoids). Abf2 is a mtDNA-binding protein, which plays a prominent role in the packaging of mtDNA into the nucleoid structure ( Basu et al, 2020 ) that protects mtDNA against damage ( Miyakawa, 2017 ). The analysis of an abf2Δ mutant showed that when grown on media containing a fermentable carbon source, cells lose mtDNA and become respiratory deficient (petite) ( Miyakawa, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Alanine Represses γ-Aminobutyric Acid Utilization and Induces Alanine Transaminase Required for Mitochondrial Function in Saccharomyces cerevisiae

et al. 2021

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The γ-aminobutyric acid (GABA) shunt constitutes a conserved metabolic route generating nicotinamide adenine dinucleotide phosphate (NADPH) and regulating stress response in most organisms. Here we show that in the presence of GABA, Saccharomyces cerevisiae produces glutamate and alanine through the irreversible action of Uga1 transaminase. Alanine induces expression of alanine transaminase (ALT1) gene. In an alt1Δ mutant grown on GABA, alanine accumulation leads to repression of the GAD1, UGA1, and UGA2 genes, involved in the GABA shunt, which could result in growth impairment. Induced ALT1 expression and negative modulation of the GABA shunt by alanine constitute a novel regulatory circuit controlling both alanine biosynthesis and catabolism. Consistent with this, the GABA shunt and the production of NADPH are repressed in a wild-type strain grown in alanine, as compared to those detected in the wild-type strain grown on GABA. We also show that heat shock induces alanine biosynthesis and ALT1, UGA1, UGA2, and GAD1 gene expression, whereas an uga1Δ mutant shows heat sensitivity and reduced NADPH pools, as compared with those observed in the wild-type strain. Additionally, an alt1Δ mutant shows an unexpected alanine-independent phenotype, displaying null expression of mitochondrial COX2, COX3, and ATP6 genes and a notable decrease in mitochondrial/nuclear DNA ratio, as compared to a wild-type strain, which results in a petite phenotype. Our results uncover a new negative role of alanine in stress defense, repressing the transcription of the GABA shunt genes, and support a novel Alt1 moonlighting function related to the maintenance of mitochondrial DNA integrity and mitochondrial gene expression.

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Section: Discussionmentioning

confidence: 99%

Alanine Represses γ-Aminobutyric Acid Utilization and Induces Alanine Transaminase Required for Mitochondrial Function in Saccharomyces cerevisiae

et al. 2021

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“…The 38th protein-humanin (encoded by 16S rRNA)-has protective activities against apoptosis-mediated diseases [37]. All other proteins required for the mitochondria regulation, maintenance and repair are encoded by the nuclear genome [38].…”

Section: Role Of Mitochondria In Pcosmentioning

confidence: 99%

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Dabravolski

Nikiforov

Eid

et al. 2021

IJMS

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Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

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“…Mitochondria are the only organelles in human cells that have their own genetic material except for the nucleus. Compared with nuclear genes, the mitochondrial genome has its specific features (5). mtDNAs exist in mitochondria and cells in multiple copies.…”

Section: Mitochondrial Geneticsmentioning

confidence: 99%

“…Except for the respiratory chain complex protein which is double-encoded by mitochondrion genome (mtDNA) and nuclear genes, all other proteins are encoded by nuclear genes. Therefore, mtDNA mutations or nuclear gene mutations may cause mitochondrial dysfunction (4,5).…”

mentioning

confidence: 99%

Mitochondrial Genome (mtDNA) and Human Diseases

Davidson¹

2021

Sci Insigt

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Mitochondria not only provide necessary energy for cells, but more importantly, they participate in the regulation of various biological functions and activities of cells. As one of the critical components of the body’s genome, mitochondrial genome (mtDNA) is the key to cell bioenergetics and genetics. However, since no protection of histones and a complete self-repair system, mtDNA is extremely prone to mutate. Human diseases caused by mtDNA mutations are only transmitted through the maternal line. The same phenotype can come from multiple mtDNA mutations, and the same mtDNA mutation can lead to multiple phenotypes. This is the major reason that makes the diagnosis and identification of mtDNA genetic diseases difficult. Meanwhile, mtDNA mutations may be the culprit involved in mediating the aging and tumorigenesis. Currently, no effective therapeutics for diseases caused by mtDNA mutations, but with the deepening of research and technological advancement, it is promising that breakthroughs in the diagnosis and treatment of mitochondrial-related diseases in the near future.

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Structure, mechanism, and regulation of mitochondrial DNA transcription initiation

Cited by 72 publications

References 226 publications

Alanine Represses γ-Aminobutyric Acid Utilization and Induces Alanine Transaminase Required for Mitochondrial Function in Saccharomyces cerevisiae

Alanine Represses γ-Aminobutyric Acid Utilization and Induces Alanine Transaminase Required for Mitochondrial Function in Saccharomyces cerevisiae

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Mitochondrial Genome (mtDNA) and Human Diseases

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