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      The hypoxia-inducible factor 1 pathway plays a critical role in the development of breast muscle myopathies in broiler chickens: a comprehensive review

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          Abstract

          In light of the increased worldwide demand for poultry meat, genetic selection efforts have intensified to produce broiler strains that grow at a higher rate, have greater breast meat yield (BMY), and convert feed to meat more efficiently. The increased selection pressure for these traits, BMY in particular, has produced multiple breast meat quality defects collectively known as breast muscle myopathies (BMM). Hypoxia has been proposed as one of the major mechanisms triggering the onset and occurrence of these myopathies. In this review, the relevant literature on the causes and consequences of hypoxia in broiler breast muscles is reviewed and discussed, with a special focus on the hypoxia-inducible factor 1 (HIF-1) pathway. Muscle fiber hypertrophy induced by selective breeding for greater BMY reduces the space available in the perimysium and endomysium for blood vessels and capillaries. The hypoxic state that results from the lack of circulation in muscle tissue activates the HIF-1 pathway. This pathway alters energy metabolism by promoting anaerobic glycolysis, suppressing the tricarboxylic acid cycle and damaging mitochondrial function. These changes lead to oxidative stress that further exacerbate the progression of BMM. In addition, activating the HIF-1 pathway promotes fatty acid synthesis, lipogenesis, and lipid accumulation in myopathic muscle tissue, and interacts with profibrotic growth factors leading to increased deposition of matrix proteins in muscle tissue. By promoting lipidosis and fibrosis, the HIF-1 pathway contributes to the development of the distinctive phenotypes of BMM, including white striations in white striping–affected muscles and the increased hardness of wooden breast–affected muscles.

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          How mitochondria produce reactive oxygen species

          The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2 •−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2 •− production within the matrix of mammalian mitochondria. The flux of O2 •− is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2 •− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD+ ratio, the extent of O2 •− production is far lower. The generation of O2 •− within the mitochondrial matrix depends critically on Δp, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2 •− generation by mitochondria in vivo from O2 •−-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2 •− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.
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            Mitochondrial fission, fusion, and stress.

            Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.
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              Mitochondrial TCA cycle metabolites control physiology and disease

              Mitochondria are signaling organelles that regulate a wide variety of cellular functions and can dictate cell fate. Multiple mechanisms contribute to communicate mitochondrial fitness to the rest of the cell. Recent evidence confers a new role for TCA cycle intermediates, generally thought to be important for biosynthetic purposes, as signaling molecules with functions controlling chromatin modifications, DNA methylation, the hypoxic response, and immunity. This review summarizes the mechanisms by which the abundance of different TCA cycle metabolites controls cellular function and fate in different contexts. We will focus on how these metabolites mediated signaling can affect physiology and disease.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/923121/overviewRole: Role: Role:
                URI : https://loop.frontiersin.org/people/2365696/overviewRole: Role: Role:
                URI : https://loop.frontiersin.org/people/1644919/overviewRole: Role: Role:
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                31 August 2023
                2023
                : 14
                : 1260987
                Affiliations
                [1] 1 Department of Animal Science , Faculty of Agricultural and Food Sciences , Université Laval , Quebec, QC, Canada
                [2] 2 Olymel S.E.C./L.P , Boucherville, QC, Canada
                [3] 3 Institute of Nutrition and Functional Foods , Université Laval , Quebec, QC, Canada
                [4] 4 Swine and Poultry Infectious Diseases Research Center , Université de Montréal , Saint-Hyacinthe, QC, Canada
                Author notes

                Edited by: Xiaofei Wang, Tennessee State University, United States

                Reviewed by: Nima Emami, Novozymes, United States

                Stephen T. Kinsey, University of North Carolina Wilmington, United States

                *Correspondence: Nabeel Alnahhas, nabeel.alnahhas@ 123456fsaa.ulaval.ca
                Article
                1260987
                10.3389/fphys.2023.1260987
                10500075
                37719466
                e5782adf-c233-4d33-95c5-fc51d24157e3
                Copyright © 2023 Alnahhas, Pouliot and Saucier.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 July 2023
                : 21 August 2023
                Funding
                Funded by: Ministère de l'Agriculture, des Pêcheries et de l'Alimentation , doi 10.13039/100008777;
                The authors declare financial support was received for the research, authorship, and/or publication of this article. This review was supported by the MAPAQ Research Chair on meat quality and safety–Musculo ( https://musculo.fsaa.ulaval.ca/) funded by the Agri-Food Innovation Partnership Program, under the Canadian Agricultural Partnership, an agreement between the governments of Canada and Quebec (Ministère de l’Agriculture des Pêcheries et de l’Alimentation du Québec MAPAQ), and by Olymel S.E.C./L.P.
                Categories
                Physiology
                Review
                Custom metadata
                Avian Physiology

                Anatomy & Physiology
                wooden breast,white striping,spaghetti meat,hypoxia,hif-1,broiler chickens
                Anatomy & Physiology
                wooden breast, white striping, spaghetti meat, hypoxia, hif-1, broiler chickens

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