Related Experiment Video
Updated: Jun 27, 2025
08:29
Analyses of Mitochondrial Calcium Influx in Isolated Mitochondria and Cultured Cells
Published on: April 27, 2018
13.8K
Mitochondrial Ca2+ Uniporter-Dependent Energetic Dysfunction Drives Hypertrophy in Heart Failure.
Hugo Alves-Figueiredo1,2,3, Christian Silva-Platas1, Manuel Estrada4
1Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Cátedra de Cardiología y Medicina Vascular, Monterrey, NL, México.
JACC. Basic to Translational Science
|April 29, 2024
Summary
The mitochondrial calcium uniporter (MCU) drives heart failure by causing cell hypertrophy and energy problems. Blocking MCU prevents these issues, offering a potential therapeutic target for heart conditions.
Area of Science:
- Cardiology
- Mitochondrial Biology
- Molecular Medicine
Background:
- The role of the mitochondrial calcium uniporter (MCU) in heart failure (HF) pathogenesis is unclear.
- Hypertrophic cardiac cells exhibit bioenergetic dysfunction and MCU overexpression.
Purpose of the Study:
- To investigate the role of MCU in angiotensin II (ANGII)-induced cardiac hypertrophy and heart failure.
- To explore the signaling pathways regulating MCU expression in cardiac hypertrophy.
Main Methods:
- Utilized angiotensin II (ANGII) to induce cardiac hypertrophy in cell and mouse models.
- Employed MCU silencing, calcium imaging, ROS detection, and Western blotting.
- Analyzed MCU expression in human heart failure patient samples and after left ventricular assist device (LVAD) implantation.
Main Results:
- Silencing MCU prevented ANGII-induced cell hypertrophy, mitochondrial dysfunction, and inflammation by blocking calcium overload.
- Identified Ca2+/calmodulin-independent protein kinase II/cyclic adenosine monophosphate response element-binding protein signaling as a regulator of ANGII-induced MCU upregulation.
- Observed increased MCU expression in mouse models of HF and human HF patients, correlating with pathological remodeling.
- Demonstrated decreased MCU expression post-LVAD implantation, indicating tissue plasticity.
Conclusions:
- MCU plays a critical role in mediating cardiac hypertrophy and bioenergetic dysfunction in heart failure.
- Targeting MCU or its regulatory pathways presents a potential therapeutic strategy for heart failure.
Related Concept Videos
01:17Pathophysiology of Heart Failure
1.6K
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
1.6K
01:26Imbalances in Cardiac Output
1.4K
The heart's primary function is to pump blood throughout the body, maintaining a balance between blood sent out (cardiac output) and blood returning (venous return). If this balance is disrupted, it can result in congestive heart failure (CHF), a severe condition where the heart becomes an inefficient pump, leading to inadequate blood circulation.
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
1.4K
01:26Cross-bridge Cycle
117.4K
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
117.4K
01:29Pathophysiology of Cardiac Performance
644
Typical heart performance is influenced by heart rate, rhythm, myocardial contraction, and metabolism or blood flow. The cardiac muscle exhibits distinct electrophysiological features, including pacemaker activity and calcium channel control, which play a vital role in the heart's response to various drugs. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, regulates heart rate. Sympathetic activation increases heart rate, while parasympathetic activation...
644
01:26Heart Failure Drugs: Inotropic Agents
574
Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
574
01:37Energy to Drive Translocation
2.1K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.1K