Article
Cardiac & Cardiovascular Systems
Luigi Ferrucci, Julian Candia, Ceereena Ubaida-Mohien, Alexey Lyashkov, Nirad Banskota, Christiaan Leeuwenburgh, Stephanie Wohlgemuth, Jack M. Guralnik, Mary Kaileh, Dongxue Zhang, Robert Sufit, Supriyo De, Myriam Gorospe, Rachel Munk, Charlotte A. Peterson, Mary M. McDermott
Summary: Transcriptomic and proteomic analyses revealed activation of hypoxia-compensatory mechanisms, inflammation, fibrosis, apoptosis, angiogenesis, unfolded protein response, and nerve and muscle repair in peripheral artery disease (PAD) muscle. Aberrant proportions of mitochondrial respiratory proteins and reduced activity of rate-limiting glycolytic enzymes were also observed. These mechanisms may serve as potential targets for disease modification.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Aranzazu M. de Maranon, Pedro Diaz-Pozo, Francisco Canet, Noelia Diaz-Morales, Zaida Abad-Jimenez, Sandra Lopez-Domenech, Teresa Vezza, Nadezda Apostolova, Carlos Morillas, Milagros Rocha, Victor M. Victor
Summary: This study examines the effect of metformin treatment on mitochondrial function and mitophagy in type 2 diabetic patients. The results show that metformin improves mitochondrial function, restores the levels of ETC complexes, enhances AMPK activation and mitophagy, and reverses the increase in inflammation markers. These findings suggest the beneficial clinical implications of metformin in the treatment of type 2 diabetes.
Article
Cardiac & Cardiovascular Systems
Mary M. McDermott, Sudarshan Dayanidhi, Kate Kosmac, Sunil Saini, Joshua Slysz, Christiaan Leeuwenburgh, Lisa Hartnell, Robert Sufit, Luigi Ferrucci
Summary: Aerobic exercise has positive effects on mitochondrial activity and muscle mass in older adults, but its impact on patients with peripheral artery disease remains unclear. Studies show that walking exercise may increase lower extremity ischemia in PAD patients, and more research is needed to clarify the underlying mechanisms.
CIRCULATION RESEARCH
(2021)
Article
Cell Biology
Palak Ahuja, Chun Fai Ng, Brian Pak Shing Pang, Wing Suen Chan, Margaret Chui Ling Tse, Xinyi Bi, Hiu-Lam Rachel Kwan, Daniel Brobst, Oana Herlea-Pana, Xiuying Yang, Guanhua Du, Suchaorn Saengnipanthkul, Hye Lim Noh, Baowei Jiao, Jason K. Kim, Chi Wai Lee, Keqiang Ye, Chi Bun Chan
Summary: The study reveals that BDNF promotes mitochondrial fission and clearance in skeletal muscle, maintaining mitochondrial quality and function. Muscle-specific bdnf knockout mice fed with a high-fat diet exhibit mitochondrial defects and metabolic disorders.
Article
Multidisciplinary Sciences
Joshua C. Drake, Rebecca J. Wilson, Rhianna C. Laker, Yuntian Guan, Hannah R. Spaulding, Anna S. Nichenko, Wenqing Shen, Huayu Shang, Maya Dorn, Kian Huang, Mei Zhang, Aloka B. Bandara, Matthew H. Brisendine, Jennifer A. Kashatus, Poonam R. Sharma, Alexander Young, Jitendra Gautam, Ruofan Cao, Horst Wallrabe, Paul A. Chang, Michael Wong, Eric M. Desjardins, Simon A. Hawley, George J. Christ, David F. Kashatus, Clint L. Miller, Matthew J. Wolf, Ammasi Periasamy, Gregory R. Steinberg, D. Grahame Hardie, Zhen Yan
Summary: Mitochondria form a complex, interconnected reticulum maintained through coordination among biogenesis, dynamic fission, fusion and mitophagy in response to various cues. Specific isoforms of AMP-activated protein kinase are localized on the outer mitochondrial membrane and vary in activation across the reticulum in response to energetic stress. The discovery highlights the complexity of sensing cellular energetics in vivo and its implications for targeting mitochondrial energetics in disease treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Geriatrics & Gerontology
Lisa Gambarotto, Samuele Metti, Martina Chrisam, Cristina Cerqua, Patrizia Sabatelli, Andrea Armani, Carlo Zanon, Marianna Spizzotin, Silvia Castagnaro, Flavie Strappazzon, Paolo Grumati, Matilde Cescon, Paola Braghetta, Eva Trevisson, Francesco Cecconi, Paolo Bonaldo
Summary: The study reveals that Ambra1 plays a critical role in the mitophagic flux of adult murine skeletal muscle and its deficiency leads to abnormal mitochondria and myofiber remodeling.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Multidisciplinary Sciences
Jacqueline E. Lebenzon, Peter W. Denezis, Lamees Mohammad, Katherine E. Mathers, Kurtis F. Turnbull, James F. Staples, Brent J. Sinclair
Summary: A study has found that dormant Colorado potato beetles achieve metabolic suppression through mitophagy, which leads to the breakdown of flight muscle mitochondria. The beetles reverse mitophagy and increase mitochondrial biogenesis at the end of diapause to replenish their flight muscle mitochondrial pools.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
HaiXu Song, Xiaoxiang Tian, Dan Liu, Meili Liu, Yanxia Liu, Jing Liu, Zhu Mei, Chenghui Yan, Yaling Han
Summary: The study established a skeletal muscle-specific CREG1 knockout mouse model, which showed effects on motor function and mitochondrial quality. Lack of CREG1 accelerated mitophagy in the skeletal muscle.
Review
Pharmacology & Pharmacy
Alexander V. Blagov, Andrey G. Goncharov, Olga O. Babich, Viktoriya V. Larina, Alexander N. Orekhov, Alexandra A. Melnichenko
Summary: This review discusses the use of mitophagy activators as a class of drug compounds for the treatment of Parkinson's disease, and explores the impact of mutations in Pink1 and Parkin enzymes on mitophagy.
Article
Biochemistry & Molecular Biology
Cui Ma, Xiaoying Wang, Siyu He, Lixin Zhang, June Bai, Lihui Qu, Jing Qi, Xiaodong Zheng, Xiangrui Zhu, Jian Mei, Xiaoyu Guan, Hao Yuan, Daling Zhu
Summary: Our study demonstrates that AIF deficiency in PASMCs leads to impaired oxidative phosphorylation, increased glycolysis, and release of ROS. AIF is downregulated and ubiquitinated under hypoxia, leading to abnormal occurrence of mitophagy and autophagy through its interaction with ubiquitin protein UBA52. Overexpressing AIF using adeno-associated virus vector protects pulmonary vascular remodeling from dysfunctional and abnormal proliferation.
CELL AND BIOSCIENCE
(2022)
Article
Cell Biology
Andrea Irazoki, Marta Martinez-Vicente, Pilar Aparicio, Cecilia Aris, Esmaeil Alibakhshi, Maria Rubio-Valera, Juan Castellanos, Luis Lores, Manuel Palacin, Anna Guma, Antonio Zorzano, David Sebastian
Summary: Sarcopenia is a major factor contributing to disability in aged individuals, with chronic inflammation playing a role in its development. The key unresolved question is the factors driving inflammation during aging and participating in sarcopenia development. Mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses, but whether accumulation of damaged mitochondria in muscle triggers inflammation during aging is still unknown.
Review
Ophthalmology
Jessica M. Skeie, Darryl Y. Nishimura, Cheryl L. Wang, Gregory A. Schmidt, Benjamin T. Aldrich, Mark A. Greiner
Summary: This article delves into the importance of mitochondrial function in aerobic eukaryotic cells, emphasizing the balance of mitochondrial dynamics and the mechanism of mitophagy. It also reviews the presence of impaired mitophagy in ocular diseases, offering insight into a potential targeted mechanism for treating ocular diseases characterized by oxidative stress and mitochondrial dysfunction.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Agnese Gugliandolo, Santino Blando, Stefano Salamone, Federica Pollastro, Emanuela Mazzon, Simone D'Angiolini
Summary: In this study, the potential protective effects of cannabinol (CBN) pre-treatment against mitochondria impairment in a Parkinson's disease model were evaluated. The results showed that CBN was able to counteract the changes in gene expression related to mitochondria function caused by neurodegeneration, particularly in the process of mitophagy mediated by PINK1/Parkin signaling pathway.
Article
Cell Biology
Sandra Franco-Iborra, Ainhoa Plaza-Zabala, Marta Montpeyo, David Sebastian, Miquel Vila, Marta Martinez-Vicente
Summary: The study found that HTT protein plays a crucial role in mitophagy, and the expansion of its polyQ tract affects this process, ultimately leading to the accumulation of damaged mitochondria and an increase in oxidative stress, leading to negative effects on mitochondrial dysfunction and neurodegeneration in Huntington disease.
Review
Physiology
Matthew H. Brisendine, Joshua C. Drake
Summary: Alzheimer's disease (AD) is the most common form of dementia, affecting approximately 6.5 million people in the US. The preclinical phase of AD is characterized by severe loss of body mass, particularly lean muscle mass and strength. Mitochondrial dysfunction in neurons and skeletal muscle has been observed in individuals with mild cognitive impairment prior to AD manifestation. Exercise has been suggested as a potential therapeutic strategy for AD due to its positive effects on mitochondria function and muscle health, but conflicting results have been found in studies involving AD patients and animal models. Further investigation is needed to explore the potential benefits of exercise in delaying or preventing the development of AD.
JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Article
Biology
Xuan Wang, Layla Parast, Larry Han, Lu Tian, Tianxi Cai
Summary: Identifying effective surrogate markers is crucial for improving clinical trial efficiency. Replacing long-term outcomes with shorter-term and/or cheaper surrogate markers can shorten study duration and reduce costs. However, methods for combining multiple markers to construct a composite marker with improved surrogacy are limited.
Article
Surgery
Madeline D. Cetlin, Tamar Polonsky, Karen Ho, Dongxue Zhang, Lu Tian, Lihui Zhao, Philip Greenland, Diane Treat-Jacobson, Melina R. Kibbe, Michael H. Criqui, Jack M. Guralnik, Mary M. McDermott
Summary: This study identified barriers to participation in supervised exercise therapy covered by CMS for lower extremity PAD. The majority of participants had never been prescribed or recommended supervised exercise therapy by their physicians, and most were unwilling or unable to pay the required copay for CMS-covered sessions. Many individuals also cited travel to medical centers as a significant obstacle to participation. These findings highlight the significant barriers faced by PAD patients in accessing and participating in supervised exercise therapy.
JOURNAL OF VASCULAR SURGERY
(2023)
Article
Peripheral Vascular Disease
Michelle Guo, Mary M. McDermott, Sudarshan Dayanidhi, Christiaan Leeuwenburgh, Stephanie Wohlgemuth, Luigi Ferrucci, Charlotte A. Peterson, Kate Kosmac, Lu Tian, Lihui Zhao, Robert Sufit, Karen Ho, Michael Criqui, Shujun Xu, Dongxue Zhang, Philip Greenland
Summary: This study evaluated the association of smoking with mitochondrial function in gastrocnemius muscle of people with peripheral artery disease (PAD). Among people with PAD, cigarette smoking may stimulate mitochondrial biogenesis to compensate for reduced oxidative capacity per unit of mitochondrial membrane, resulting in no difference in overall mitochondrial oxidative capacity according to current smoking status. However, these results were cross-sectional and a longitudinal study is needed.
Review
Cardiac & Cardiovascular Systems
Xuan Wang, Brian Lee Claggett, Lu Tian, Marcus Vinicius Bolivar Malachias, Marc A. Pfeffer, Lee-Jen Wei
Summary: For personalized or stratified medicine, it is crucial to establish a reliable and efficient prediction model for a clinical outcome of interest. However, commonly used metrics like C statistics do not accurately assess the model's prediction accuracy. This article highlights the importance of finding a clinically interpretable measure that quantifies prediction accuracy for improved model selection and evaluation.
Article
Cell Biology
Anna Picca, Matthew Triolo, Stephanie E. E. Wohlgemuth, Matthew S. S. Martenson, Robert T. T. Mankowski, Stephen D. D. Anton, Emanuele Marzetti, Christiaan Leeuwenburgh, David A. A. Hood
Summary: Altered mitochondrial quality in muscle may contribute to age-related decline in physical function. This study investigated the relationship between autophagy, mitophagy, lysosomal markers and measures of physical performance and lower extremity tissue composition in young and older adults. The results revealed that older adults had smaller muscle volume, lower tissue composition index, and higher protein content of p62 and BNIP3. The expression levels of p62 and BNIP3 were negatively correlated with the tissue composition index and performance on the 5-time sit-to-stand test. These findings suggest that dysfunction in the autophagy/mitophagy-lysosomal system is associated with deterioration of lower extremity tissue composition and muscle dysfunction.
Editorial Material
Cell Biology
Anna Picca, Emanuele Marzetti, Christiaan Leeuwenburgh
Article
Nutrition & Dietetics
Dongyu Zhang, Kori A. Spiropoulos, Akemi Wijayabahu, Demetra D. Christou, Shama D. Karanth, Stephen D. Anton, Christiaan Leeuwenburgh, Muxuan Liang, Meghann Wheeler, Danting Yang, Aduse-Poku Livingstone, Robert T. Mankowski, Ting -Yuan David Cheng, Hanchao Zhang, Erin M. Siegel, Frank J. Penedo, Jonathan D. Licht, Dejana Braithwaite
Summary: This study aimed to investigate the effects of low muscle mass (LMM) on the risk of all-cause and cardiovascular disease (CVD)-specific mortality in cancer survivors. The results showed that LMM was positively associated with the risk of all-cause and CVD-specific mortality in cancer survivors.
Article
Biochemistry & Molecular Biology
Robert T. Mankowski, Stephanie E. Wohlgemuth, Guilherme Bresciani, A. Daniel Martin, George Arnaoutakis, Tomas Martin, Eric Jeng, Leonardo Ferreira, Tiago Machuca, Mindaugas Rackauskas, Ashley J. Smuder, Thomas Beaver, Christiaan Leeuwenburgh, Barbara K. Smith
Summary: Mechanical ventilation during cardiothoracic surgery can lead to ventilator-induced diaphragm dysfunction (VIDD) and delay recovery. In this study, intraoperative phrenic nerve stimulation was performed to offset VIDD and investigate changes in mitochondrial function.
Letter
Medicine, General & Internal
Ananya Das, Timothy A. Lin, Christine Lin, Tomer Meirson, Zachary R. McCaw, Lu Tian, Ethan B. Ludmir
Article
Clinical Neurology
Menglan Pang, Audrey Gabelle, Paramita Saha-Chaudhuri, Willem Huijbers, Arie Gafson, Paul M. Matthews, Lu Tian, Ivana Rubino, Richard Hughes, Carl de Moor, Shibeshih Belachew, Changyu Shen
Summary: This study provides a proof of concept for precision medicine in future research and drug development for Alzheimer's disease through individual treatment response analysis.
ALZHEIMERS & DEMENTIA
(2023)
Article
Oncology
Linfeng Chen, Qiming Tang, Keying Zhang, Qianyang Huang, Yun Ding, Bo Jin, Szumam Liu, Kuoyuan Hwa, C. James Chou, Yani Zhang, Sheeno Thyparambil, Weili Liao, Zhi Han, Richard Mortensen, James Schilling, Zhen Li, Robert Heaton, Lu Tian, Harvey J. Cohen, Karl G. Sylvester, Rebecca C. Arent, Xinyang Zhao, Doff B. Mcelhinney, Yumei Wu, Wenpei Bai, Xuefeng B. Ling
Summary: This study explores the potential use of metabolic changes as biomarkers for assessing ovarian cancer. The research identifies key gene expression pathways and proposes symmetric dimethylarginine (SDMA) and arginine as potential liquid biopsy biomarkers for ovarian cancer assessment.
Editorial Material
Urology & Nephrology
Vivek Charu, Lu Tian, Manjula Kurella Tamura, Maria E. Montez-Rath
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lauren T. T. Wesolowski, Jessica L. L. Simons, Pier L. L. Semanchik, Mariam A. A. Othman, Joo-Hyun Kim, John M. M. Lawler, Khaled Y. Y. Kamal, Sarah H. H. White-Springer
Summary: Mechanical unloading during microgravity leads to muscle atrophy and impaired mitochondrial energetics. This study demonstrates that the SIRT1 activator, SRT2104, can preserve mitochondrial function in unloaded skeletal muscle, promoting necessary energy production and potentially supporting healthy muscle cells in microgravity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Layla Parast, Lu Tian, Tianxi Cai, Latha P. Palaniappan
Summary: This study compared the effectiveness of five surrogate markers - HbA1c, fasting glucose, 2-hour postchallenge glucose, TyG index, and HOMA-IR - in predicting the reduction of type 2 diabetes mellitus risk. The results showed that glucose and HOMA-IR were the superior surrogate markers compared to the other markers.
BMJ OPEN DIABETES RESEARCH & CARE
(2023)
Article
Medicine, General & Internal
Neela D. Thangada, Dongxue Zhang, Lu Tian, Lihui Zhao, W. Jack Rejeski, Karen J. Ho, Luigi Ferrucci, Bonnie Spring, Melina R. Kibbe, Tamar S. Polonsky, Michael H. Criqui, Mary M. Mcdermott
Summary: In this meta-analysis of individual participant data, home-based walking exercise was found to improve 6-minute walk more than supervised treadmill exercise in people with PAD. These findings support home-based walking exercise as a first-line therapy for walking limitations in PAD.