Mitochondrial Gene Expression: A Playground of Evolutionary Tinkering

Neupert, Walter

doi:10.1146/annurev-biochem-011116-110824

Cited by 28 publications

(9 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To further examine whether the improved OXPHOS activity was due to recovery of impaired mitochondrial OXPHOS electron transport chain (ETC) complexes, considering that the complex subunits are encoded by either the nuclear genome or the mitochondrial DNA (mtDNA) 69 , 70 , we separately investigated expression levels of genes of these 2 categories to see whether RESV facilitated mitochondrial non-autonomous and/or autonomous recovery. Gene representatives encoding subunits of each of the 5 ETC complexes were selected for analysis accordingly 26 .…”

Section: Resultsmentioning

confidence: 99%

Resveratrol counteracts bone loss via mitofilin-mediated osteogenic improvement of mesenchymal stem cells in senescence-accelerated mice

Yang

Sui

et al. 2018

Theranostics

View full text Add to dashboard Cite

Rational: Senescence of mesenchymal stem cells (MSCs) and the related functional decline of osteogenesis have emerged as the critical pathogenesis of osteoporosis in aging. Resveratrol (RESV), a small molecular compound that safely mimics the effects of dietary restriction, has been well documented to extend lifespan in lower organisms and improve health in aging rodents. However, whether RESV promotes function of senescent stem cells in alleviating age-related phenotypes remains largely unknown. Here, we intend to investigate whether RESV counteracts senescence-associated bone loss via osteogenic improvement of MSCs and the underlying mechanism.Methods: MSCs derived from bone marrow (BMMSCs) and the bone-specific, senescence-accelerated, osteoblastogenesis/osteogenesis-defective mice (the SAMP6 strain) were used as experimental models. In vivo application of RESV was performed at 100 mg/kg intraperitoneally once every other day for 2 months, and in vitro application of RESV was performed at 10 μM. Bone mass, bone formation rates and osteogenic differentiation of BMMSCs were primarily evaluated. Metabolic statuses of BMMSCs and the mitochondrial activity, transcription and morphology were also examined. Mitofilin expression was assessed at both mRNA and protein levels, and short hairpin RNA (shRNA)-based gene knockdown was applied for mechanistic experiments.Results: Chronic intermittent application of RESV enhances bone formation and counteracts accelerated bone loss, with RESV improving osteogenic differentiation of senescent BMMSCs. Furthermore, in rescuing osteogenic decline under BMMSC senescence, RESV restores cellular metabolism through mitochondrial functional recovery via facilitating mitochondrial autonomous gene transcription. Molecularly, in alleviating senescence-associated mitochondrial disorders of BMMSCs, particularly the mitochondrial morphological alterations, RESV upregulates Mitofilin, also known as inner membrane protein of mitochondria (Immt) or Mic60, which is the core component of the mitochondrial contact site and cristae organizing system (MICOS). Moreover, Mitofilin is revealed to be indispensable for mitochondrial homeostasis and osteogenesis of BMMSCs, and that insufficiency of Mitofilin leads to BMMSC senescence and bone loss. More importantly, Mitofilin mediates resveratrol-induced mitochondrial and osteogenic improvements of BMMSCs in senescence.Conclusion: Our findings uncover osteogenic functional improvements of senescent MSCs as critical impacts in anti-osteoporotic practice of RESV, and unravel Mitofilin as a novel mechanism mediating RESV promotion on mitochondrial function in stem cell senescence.

show abstract

Section: Resultsmentioning

confidence: 99%

Resveratrol counteracts bone loss via mitofilin-mediated osteogenic improvement of mesenchymal stem cells in senescence-accelerated mice

Yang

Sui

et al. 2018

Theranostics

View full text Add to dashboard Cite

show abstract

“…The mammalian mitochondrial genome encodes 13 peptides that are core components of the OXPHOS system ( Neupert, 2016 ). Loss of SHMT2 reduces cellular deoxynucleotide pool ( Ducker et al, 2016 ), which can be associated with mtDNA depletion ( Bourdon et al, 2007 ; Suomalainen & Battersby, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Serine catabolism is essential to maintain mitochondrial respiration in mammalian cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Consistent with previous studies [ 15 ], the proteins from the mitochondrion (88,405 proteins from 6119 species) and chloroplast (80,807 proteins form 935 species) sets have relatively low disorder contents compared to the proteins encoded in nuclear genes of eukaryotic organisms, for example, the mitochondrial protein set has a considerably lower disorder content of 8.6% at protein level. The mitochondria have lost most of their ancestral genes either by transferring to the nucleus or by being discarded [ 31 ]. Here, we show that the mitochondrial proteins have relatively low disorder contents (i.e., highly ordered) at both the protein and the residue levels ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins

Guo

Tuskan

et al. 2018

International Journal of Genomics

View full text Add to dashboard Cite

The existence of complete genome sequences makes it important to develop different approaches for classification of large-scale data sets and to make extraction of biological insights easier. Here, we propose an approach for classification of complete proteomes/protein sets based on protein distributions on some basic attributes. We demonstrate the usefulness of this approach by determining protein distributions in terms of two attributes: protein lengths and protein intrinsic disorder contents (ID). The protein distributions based on L and ID are surveyed for representative proteome organisms and protein sets from the three domains of life. The two-dimensional maps (designated as fingerprints here) from the protein distribution densities in the LD space defined by ln(L) and ID are then constructed. The fingerprints for different organisms and protein sets are found to be distinct with each other, and they can therefore be used for comparative studies. As a test case, phylogenetic trees have been constructed based on the protein distribution densities in the fingerprints of proteomes of organisms without performing any protein sequence comparison and alignments. The phylogenetic trees generated are biologically meaningful, demonstrating that the protein distributions in the LD space may serve as unique phylogenetic signals of the organisms at the proteome level.

show abstract

Mitochondrial Gene Expression: A Playground of Evolutionary Tinkering

Abstract: This article introduces the Mitochondria theme of the Annual Review of Biochemistry, Volume 85.

Cited by 28 publications

References 12 publications

Resveratrol counteracts bone loss via mitofilin-mediated osteogenic improvement of mesenchymal stem cells in senescence-accelerated mice

Resveratrol counteracts bone loss via mitofilin-mediated osteogenic improvement of mesenchymal stem cells in senescence-accelerated mice

Serine catabolism is essential to maintain mitochondrial respiration in mammalian cells

Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins

Contact Info

Product

Resources

About