About the research:
The heart is capable of adapting to stress situations through a process of structural and molecular remodeling. Although initially adaptive, the sustained activation of this response becomes deleterious and can lead to heart failure (HF). The signals that regulate this response are poorly understood; however, there is great interest in identifying them to explore their therapeutic potential. During physical exercise, skeletal muscle secretes the metabolite succinate. While a transient rise in succinate contributes to the adaptive response induced by exercise in distal tissues, its sustained elevation has the opposite effect, increasing the risk of HF. Our project will test the hypothesis that succinate regulates cardiac remodeling, with the type of response (adaptive or maladaptive) depending on whether its elevation is transient or sustained.
Selected publications:
Xiao H, Bozi LHM, Sun Y, Riley CL, Philip VM, Chen M, Li J, Zhang T, Mills EL, Emont MP, Sun W, Reddy A, Garrity R, Long J, Becher T, Vitas LP, Laznik-Bogoslavski D, Ordonez M, Liu X, Chen X, Wang Y, Liu W, Tran N, Liu Y, Zhang Y, Cypess AM, White AP, He Y, Deng R, Schöder H, Paulo JA, Jedrychowski MP, Banks AS, Tseng YH, Cohen P, Tsai LT, Rosen ED, Klein S, Chondronikola M, McAllister FE, Van Bruggen N, Huttlin EL, Spiegelman BM, Churchill GA, Gygi SP, Chouchani ET. Architecture of the outbred brown fat proteome defines regulators of metabolic physiology. Cell. 2022 Nov 23;185(24):4654-4673.e28. doi: 10.1016/j.cell.2022.10.003. Epub 2022 Nov 4. PMID: 36334589; PMCID: PMC10040263.
Reddy A, Bozi LHM, Yaghi OK, Mills EL, Xiao H, Nicholson HE, Paschini M, Paulo JA, Garrity R, Laznik-Bogoslavski D, Ferreira JCB, Carl CS, Sjøberg KA, Wojtaszewski JFP, Jeppesen JF, Kiens B, Gygi SP, Richter EA, Mathis D, Chouchani ET. pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise. Cell. 2020 Oct 1;183(1):62-75.e17. doi: 10.1016/j.cell.2020.08.039. Epub 2020 Sep 17. PMID: 32946811; PMCID: PMC7778787.
Bozi LH, Jannig PR, Rolim N, Voltarelli VA, Dourado PM, Wisløff U, Brum PC. Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats. J Cell Mol Med. 2016 Nov;20(11):2208-2212. doi: 10.1111/jcmm.12894. Epub 2016 Jun 16. PMID: 27305869; PMCID: PMC5082404.
Campos JC, Marchesi Bozi LH, Krum B, Grassmann Bechara LR, Ferreira ND, Arini GS, Albuquerque RP, Traa A, Ogawa T, van der Bliek AM, Beheshti A, Chouchani ET, Van Raamsdonk JM, Blackwell TK, Ferreira JCB. Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics. Proc Natl Acad Sci U S A. 2023 Jan 10;120(2):e2204750120. doi: 10.1073/pnas.2204750120. Epub 2023 Jan 3. PMID: 36595699; PMCID: PMC9926278.
