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Article ; Online: OXPHOS deficiencies affect peroxisome proliferation by downregulating genes controlled by the SNF1 signaling pathway

Jean-Claude Farre / Krypton Carolino / Lou Devanneaux / Suresh Subramani

eLife, Vol

2022 Volume 11

Abstract: How environmental cues influence peroxisome proliferation, particularly through organelles, remains largely unknown. Yeast peroxisomes metabolize fatty acids (FA), and methylotrophic yeasts also metabolize methanol. NADH and acetyl-CoA, produced by these ...

Abstract	How environmental cues influence peroxisome proliferation, particularly through organelles, remains largely unknown. Yeast peroxisomes metabolize fatty acids (FA), and methylotrophic yeasts also metabolize methanol. NADH and acetyl-CoA, produced by these pathways enter mitochondria for ATP production and for anabolic reactions. During the metabolism of FA and/or methanol, the mitochondrial oxidative phosphorylation (OXPHOS) pathway accepts NADH for ATP production and maintains cellular redox balance. Remarkably, peroxisome proliferation in Pichia pastoris was abolished in NADH-shuttling- and OXPHOS mutants affecting complex I or III, or by the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), indicating ATP depletion causes the phenotype. We show that mitochondrial OXPHOS deficiency inhibits expression of several peroxisomal proteins implicated in FA and methanol metabolism, as well as in peroxisome division and proliferation. These genes are regulated by the Snf1 complex (SNF1), a pathway generally activated by a high AMP/ATP ratio. In OXPHOS mutants, Snf1 is activated by phosphorylation, but Gal83, its interacting subunit, fails to translocate to the nucleus. Phenotypic defects in peroxisome proliferation observed in the OXPHOS mutants, and phenocopied by the Δgal83 mutant, were rescued by deletion of three transcriptional repressor genes (MIG1, MIG2, and NRG1) controlled by SNF1 signaling. Our results are interpreted in terms of a mechanism by which peroxisomal and mitochondrial proteins and/or metabolites influence redox and energy metabolism, while also influencing peroxisome biogenesis and proliferation, thereby exemplifying interorganellar communication and interplay involving peroxisomes, mitochondria, cytosol, and the nucleus. We discuss the physiological relevance of this work in the context of human OXPHOS deficiencies.
Keywords	peroxisome proliferation ; mitochondria ; OXPHOS ; SNF1 ; interorganelle communication ; feedback loop ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Roles of Ubiquitin-Binding Protein Shuttles in the Degradative Fate of Ubiquitinated Proteins in the Ubiquitin-Proteasome System and Autophagy

Katarzyna Zientara-Rytter / Suresh Subramani

Cells, Vol 8, Iss 1, p

2019 Volume 40

Abstract: The ubiquitin-proteasome system (UPS) and autophagy are the two major intracellular protein quality control (PQC) pathways that are responsible for cellular proteostasis (homeostasis of the proteome) by ensuring the timely degradation of misfolded, ... ...

Abstract	The ubiquitin-proteasome system (UPS) and autophagy are the two major intracellular protein quality control (PQC) pathways that are responsible for cellular proteostasis (homeostasis of the proteome) by ensuring the timely degradation of misfolded, damaged, and unwanted proteins. Ubiquitination serves as the degradation signal in both these systems, but substrates are precisely targeted to one or the other pathway. Determining how and when cells target specific proteins to these two alternative PQC pathways and control the crosstalk between them are topics of considerable interest. The ubiquitin (Ub) recognition code based on the type of Ub-linked chains on substrate proteins was believed to play a pivotal role in this process, but an increasing body of evidence indicates that the PQC pathway choice is also made based on other criteria. These include the oligomeric state of the Ub-binding protein shuttles, their conformation, protein modifications, and the presence of motifs that interact with ATG8/LC3/GABARAP (autophagy-related protein 8/microtubule-associated protein 1A/1B-light chain 3/GABA type A receptor-associated protein) protein family members. In this review, we summarize the current knowledge regarding the Ub recognition code that is bound by Ub-binding proteasomal and autophagic receptors. We also discuss how cells can modify substrate fate by modulating the structure, conformation, and physical properties of these receptors to affect their shuttling between both degradation pathways.
Keywords	ubiquitin-proteasome system ; selective autophagy ; proteostasis ; protein quality control ; ubiquitination ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: BiFC Method Based on Intraorganellar Protein Crowding Detects Oleate-Dependent Peroxisomal Targeting of Pichia pastoris Malate Dehydrogenase

Jean-Claude Farré / Paul Li / Suresh Subramani

International Journal of Molecular Sciences, Vol 22, Iss 4890, p

2021 Volume 4890

Abstract: The maintenance of intracellular NAD + /NADH homeostasis across multiple, subcellular compartments requires the presence of NADH-shuttling proteins, which circumvent the lack of permeability of organelle membranes to these cofactors. Very little is known ...

Abstract	The maintenance of intracellular NAD + /NADH homeostasis across multiple, subcellular compartments requires the presence of NADH-shuttling proteins, which circumvent the lack of permeability of organelle membranes to these cofactors. Very little is known regarding these proteins in the methylotrophic yeast, Pichia pastoris . During the study of the subcellular locations of these shuttling proteins, which often have dual subcellular locations, it became necessary to develop new ways to detect the weak peroxisomal locations of some of these proteins. We have developed a novel variation of the traditional Bimolecular Fluorescence Complementation (BiFC), called divergent BiFC, to detect intraorganellar colocalization of two noninteracting proteins based on their proximity-based protein crowding within a small subcellular compartment, rather than on the traditional protein–protein interactions expected for BiFC. This method is used to demonstrate the partially peroxisomal location of one such P. pastoris NADH-shuttling protein, malate dehydrogenase B, only when cells are grown in oleate, but not when grown in methanol or glucose. We discuss the mode of NADH shuttling in P. pastoris and the physiological basis of the medium-dependent compartmentalization of Pp MdhB.
Keywords	redox balance ; NADH shuttle ; peroxisomal malate dehydrogenase ; environment-dependent peroxisomal targeting ; intraorganellar protein crowding ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	612
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aeroplane wing, a new recessive autosomal phenotypic marker in the malaria vector, Anopheles stephensi Liston

Chaitali Ghosh / M. Soumya / Naveen Kumar / Chethan Kumar R / Soumya Gopal Joshi / Sampath Kumar / Suresh Subramani / Sunita Swain

Heliyon, Vol 10, Iss 1, Pp e23693- (2024)

1481

Abstract: A novel and distinct mutant with a phenotype, aeroplane wing (ae) is reported for the first time in the urban malaria vector Anopheles stephensi. The main aim of this study was to establish the mode of inheritance of the ae gene performing genetic ... ...

Abstract	A novel and distinct mutant with a phenotype, aeroplane wing (ae) is reported for the first time in the urban malaria vector Anopheles stephensi. The main aim of this study was to establish the mode of inheritance of the ae gene performing genetic crossings between the mutants and wild types. These mutants show extended open wings that are visible to naked eyes in both the sexes. Mutants were first noticed in a nutritionally stressed isofemale colony. Strategic genetic crosses revealed that the ae gene is a recessive, autosomal, and monogenic trait having full penetrance with uniform expression in its adult stage. Egg morphometric analysis confirmed that these mutants were intermediate variant. No significant differences were observed in the wing venation and size of ae mutants compared to their control parental lines. Further cytogenetic analysis on the ovarian polytene chromosome of ae mutant showed an inversion (3Li) on the 3L arm like its parental line. This ae mutant would be a prominent marker and could be useful to study the functions of related specific genes within its genome.
Keywords	Anopheles stephensi ; Aeroplane wings ; mutant ; Crossbreeding ; Autosomal ; Recessive ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	580
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Recognition and Chaperoning by Pex19, Followed by Trafficking and Membrane Insertion of the Peroxisome Proliferation Protein, Pex11

Katarzyna M. Zientara-Rytter / Shanmuga S. Mahalingam / Jean-Claude Farré / Krypton Carolino / Suresh Subramani

Cells, Vol 11, Iss 157, p

2022 Volume 157

Abstract: Pex11, an abundant peroxisomal membrane protein (PMP), is required for division of peroxisomes and is robustly imported to peroxisomal membranes. We present a comprehensive analysis of how the Pichia pastoris Pex11 is recognized and chaperoned by Pex19, ... ...

Abstract	Pex11, an abundant peroxisomal membrane protein (PMP), is required for division of peroxisomes and is robustly imported to peroxisomal membranes. We present a comprehensive analysis of how the Pichia pastoris Pex11 is recognized and chaperoned by Pex19, targeted to peroxisome membranes and inserted therein. We demonstrate that Pex11 contains one Pex19-binding site (Pex19-BS) that is required for Pex11 insertion into peroxisomal membranes by Pex19, but is non-essential for peroxisomal trafficking. We provide extensive mutational analyses regarding the recognition of Pex19-BS in Pex11 by Pex19. Pex11 also has a second, Pex19-independent membrane peroxisome-targeting signal (mPTS) that is preserved among Pex11-family proteins and anchors the human HsPex11γ to the outer leaflet of the peroxisomal membrane. Thus, unlike most PMPs, Pex11 can use two mechanisms of transport to peroxisomes, where only one of them depends on its direct interaction with Pex19, but the other does not. However, Pex19 is necessary for membrane insertion of Pex11. We show that Pex11 can self-interact, using both homo- and/or heterotypic interactions involving its N-terminal helical domains. We demonstrate that Pex19 acts as a chaperone by interacting with the Pex19-BS in Pex11, thereby protecting Pex11 from spontaneous oligomerization that would otherwise cause its aggregation and subsequent degradation.
Keywords	peroxisomal membrane protein ; peroxisome proliferation protein ; peroxisome division ; Pex11 ; Pex19 ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Mahul Chakraborty / Arunachalam Ramaiah / Adriana Adolfi / Paige Halas / Bhagyashree Kaduskar / Luna Thanh Ngo / Suvratha Jayaprasad / Kiran Paul / Saurabh Whadgar / Subhashini Srinivasan / Suresh Subramani / Ethan Bier / Anthony A. James / J. J. Emerson

BMC Biology, Vol 20, Iss 1, Pp 1-

Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly

2022 Volume 2

Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of a TNF-TNFR-like system in malaria vectors (Anopheles stephensi) likely to influence Plasmodium resistance

Subhashini Srinivasan / Chaitali Ghosh / Shrestha Das / Aditi Thakare / Siddharth Singh / Apoorva Ganesh / Harsh Mahawar / Aadhya Jaisimha / Mohanapriya Krishna / Aritra Chattopadhyay / Rishima Borah / Vikrant Singh / Soumya M / Naveen Kumar / Sampath Kumar / Sunita Swain / Suresh Subramani

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 13

Abstract: Abstract Identification of Plasmodium-resistance genes in malaria vectors remains an elusive goal despite the recent availability of high-quality genomes of several mosquito vectors. Anopheles stephensi, with its three distinctly-identifiable forms at ... ...

Abstract	Abstract Identification of Plasmodium-resistance genes in malaria vectors remains an elusive goal despite the recent availability of high-quality genomes of several mosquito vectors. Anopheles stephensi, with its three distinctly-identifiable forms at the egg stage, correlating with varying vector competence, offers an ideal species to discover functional mosquito genes implicated in Plasmodium resistance. Recently, the genomes of several strains of An. stephensi of the type-form, known to display high vectorial capacity, were reported. Here, we report a chromosomal-level assembly of an intermediate-form of An. stephensi strain (IndInt), shown to have reduced vectorial capacity relative to a strain of type-form (IndCh). The contig level assembly with a L50 of 4 was scaffolded into chromosomes by using the genome of IndCh as the reference. The final assembly shows a heterozygous paracentric inversion, 3Li, involving 8 Mbp, which is syntenic to the extensively-studied 2La inversion implicated in Plasmodium resistance in An. gambiae involving 21 Mbp. Deep annotation of genes within the 3Li region in the IndInt assembly using the state-of-the-art protein-fold prediction and other annotation tools reveals the presence of a tumor necrosis factor-alpha (TNF-alpha) like gene, which is the homolog of the Eiger gene in Drosophila. Subsequent chromosome-wide searches revealed homologs of Wengen (Wgn) and Grindelwald (Grnd) genes, which are known to be the receptors for Eiger in Drosophila. We have identified all the genes in IndInt required for Eiger-mediated signaling by analogy to the TNF-alpha system, suggesting the presence of a functionally-active Eiger signaling pathway in IndInt. Comparative genomics of the three type-forms with that of IndInt, reveals structurally disruptive mutations in Eiger gene in all three strains of the type-form, suggesting compromised innate immunity in the type-form as the likely cause of high vectorial capacity in these strains. This is the first report of the presence of a homolog of ...
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity

Aditi Thakare / Chaitali Ghosh / Tejashwini Alalamath / Naveen Kumar / Himani Narang / Saurabh Whadgar / Kiran Paul / Shweta Shrotri / Sampath Kumar / M. Soumya / Raksha Rao / Mahul Chakraborty / Bibha Choudhary / Susanta K. Ghosh / Suresh Subramani / Sunita Swain / Subhashini Srinivasan

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 16

Abstract: Abstract Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water ...

Abstract	Abstract Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2Rb genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+b/2Rb) and UCI (2Rb/2Rb), IndCh is found to be homozygous for the standard form (2R+b/2R+b). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2Rb. The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi, putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Radiological factors affecting post-operative global coronal balance in Lenke 5 C scoliosis.

Shetty, Ajoy Prasad / Suresh, Subramani / Aiyer, Siddharth N / Kanna, Rishi / Rajasekaran, Shanmuganathan

Journal of spine surgery (Hong Kong)

2017 Volume 3, Issue 4, Page(s) 541–547

Abstract: Background: Lenke 5 C curves are frequently associated with clinically and radiological coronal imbalance. Appropriate selection of proximal and distal levels of fusion is essential to ensure good coronal balance (CB). We aimed to evaluate radiological ... ...

Abstract	Background: Lenke 5 C curves are frequently associated with clinically and radiological coronal imbalance. Appropriate selection of proximal and distal levels of fusion is essential to ensure good coronal balance (CB). We aimed to evaluate radiological factors associated with (I) global CB in the early post-operative period; (II) late decompensation of CB; and (III) favourable spontaneous correction of CB on long term follow up. Methods: Twenty-three Lenke type 5C scoliosis cases treated with selective posterior lumbar instrumentation were retrospectively evaluated. Pre-operative, early post-operative and late post-operative (>2 years) whole length radiographs were analysed. Cobb's angle, lumbar lordosis, coronal imbalance, lower instrumented vertebra (LIV) tilt and translation and upper instrumented vertebra (UIV) tilt and translation were measured. The proximal and distal fusion levels were noted and correlated with post-operative CB. Results: There were 21 females and 2 males with a mean follow up of 36 months. The mean pre-operative cobb angle was 55°±13.26°, which corrected to 14.7°±8.84° and was maintained on follow up. Eight patients had early post-operative coronal imbalance with spontaneous resolution seen in six cases on long term follow-up. At final follow-up, four cases had coronal imbalance (persistent imbalance since early post-operative period =2; late decompensation =2). In cases with early imbalance 5/8 cases had a pre-operative LIV tilt of ≥25°. All four patients with coronal imbalance at final follow-up had pre-operative LIV tilt ≥25°. Radiographic parameters which correlated with post-operative coronal imbalance were pre-operative LIV tilt (r=0.64, P=0.001), pre-operative LIV translation (r=0.696, P<0.001), pre-operative UIV translation (r=0.44, P=0.030), post-operative LIV tilt (r=0.804, P<0.001), and post-operative UIV tilt (r=0.62, P=0.001). Conclusions: In Lenke 5C scoliosis, a pre-operative LIV tilt ≥25° significantly correlates with post-operative global coronal imbalance. Increasing UIV tilt may be a factor that accounts for improvement of CB in late follow-up period.
Language	English
Publishing date	2017-11-16
Publishing country	China
Document type	Journal Article
ZDB-ID	2874556-5
ISSN	2414-4630 ; 2414-469X
ISSN (online)	2414-4630
ISSN	2414-469X
DOI	10.21037/jss.2017.09.04
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pexophagy

Suresh Subramani / Sarah F. Burnett / Ronak Lakhani / Andreas Till

International Journal of Cell Biology, Vol

The Selective Degradation of Peroxisomes

2012 Volume 2012

Keywords	Cytology ; QH573-671 ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Cytology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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