Human Heart Failure Alters Mitochondria and Fiber 3D Structure Triggering Metabolic Shifts

Zer Vue; Peter T Ajayi; Kit Neikirk; Alexandria C Murphy; Praveena Prasad; Brenita C Jenkins; Larry Vang; Edgar Garza-Lopez; Margaret Mungai; Andrea G Marshall; Heather K Beasley; Mason Killion; Remi Parker; Josephs Anukodem; Kory Lavine; Olujimi Ajijola; Bret C Mobley; Dao-Fu Dai; Vernat Exil; Annet Kirabo; Yan Ru Su; Kelsey Tomasek; Xiuqi Zhang; Celestine Wanjalla; David L Hubert; Mark A Phillips; Jian-Qiang Shao; Melanie R McReynolds; Brian Glancy; Antentor Hinton Jr

doi:10.1101/2023.11.28.569095

Human Heart Failure Alters Mitochondria and Fiber 3D Structure Triggering Metabolic Shifts

bioRxiv [Preprint]. 2023 Dec 14:2023.11.28.569095. doi: 10.1101/2023.11.28.569095.

Authors

Zer Vue¹, Peter T Ajayi², Kit Neikirk¹, Alexandria C Murphy³, Praveena Prasad³, Brenita C Jenkins³, Larry Vang¹, Edgar Garza-Lopez⁴, Margaret Mungai¹, Andrea G Marshall¹, Heather K Beasley¹, Mason Killion¹, Remi Parker¹, Josephs Anukodem¹, Kory Lavine⁵, Olujimi Ajijola⁶, Bret C Mobley⁷, Dao-Fu Dai⁸, Vernat Exil⁹, Annet Kirabo¹⁰, Yan Ru Su¹¹, Kelsey Tomasek¹¹, Xiuqi Zhang¹¹, Celestine Wanjalla¹¹, David L Hubert¹², Mark A Phillips¹², Jian-Qiang Shao¹³, Melanie R McReynolds³, Brian Glancy^{2

14}, Antentor Hinton Jr¹

Affiliations

¹ Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.
² Muscle Energetics Laboratory, NHLBI, NIH, Bethesda, MD, 20892, USA.
³ Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801.
⁴ Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
⁵ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁶ UCLA Cardiac Arrhythmia Center, University of California, Los Angeles, CA, USA.
⁷ Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, 37232 USA.
⁸ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Department of Pediatrics, Div. of Cardiology, St. Louis University School of Medicine, St. Louis, MO, 63104, USA.
¹⁰ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹¹ Department of Medicine, Division of Infectious Diseases, Vanderbilt University, Nashville, TN, 37232, USA.
¹² Department of Integrative Biology, Oregon State University, Corvallis, OR, 97331, USA.
¹³ Central Microscopy Research Facility, Iowa City, IA 52242, USA.
¹⁴ NIAMS, NIH, Bethesda, MD, 20892, USA.

Abstract

This study, utilizing SBF-SEM, reveals structural alterations in mitochondria and myofibrils in human heart failure (HF). Mitochondria in HF show changes in structure, while myofibrils exhibit increased cross-sectional area and branching. Metabolomic and lipidomic analyses indicate concomitant dysregulation in key pathways. The findings underscore the need for personalized treatments considering individualized structural changes in HF.

Keywords: 3D reconstruction; MICOS complex; Mitochondria; heart failure; myofibril.

Publication types

Preprint

Abstract

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