Energetic Interactions Between Subcellular Organelles in Striated Muscles

Jérôme Piquereau¹, Vladimir Veksler¹, Marta Novotova²

¹Université Paris-Saclay, Inserm, UMR-S 1180, Châtenay-Malabry, France.

Frontiers in Cell and Developmental Biology

|November 2, 2020

Summary

Striated muscle cells, such as those in the heart and skeletal muscles, have a complex system for delivering energy to where it's needed most. This study explores two main energy transfer mechanisms: phosphotransfer kinases like creatine kinase (CK) and direct adenine nucleotide channeling (DANC). CK shuttles energy through chemical reactions, while DANC directly transfers ATP and ADP between mitochondria and ATPases. The research shows that when the CK system is impaired, DANC becomes more important. Mitochondria are organized in specific patterns during development, and this organization is crucial for efficient energy transfer. In heart failure, cellular disorganization and reduced mitochondrial mass impair both DANC and CK systems, leading to energy deficiency and reduced muscle function. The study highlights the importance of maintaining cell structure for effective energy supply in striated muscles.

Area of Science:

Cellular bioenergetics in muscle physiology
Mitochondrial function in cardiac and skeletal muscle
Metabolic pathways in striated muscle

Background:

Striated muscle cells are highly specialized with limited cytosol and dense organelle packing. These cells require fluctuating energy supplies, primarily from oxidative metabolism. Mitochondria generate ATP, but efficient delivery to ATPases is essential. Prior research has shown that phosphotransfer kinases help shuttle energy. However, the role of direct adenine nucleotide channeling (DANC) remains unclear. This gap motivated investigation into how energy transfer mechanisms adapt during development and disease. No prior work had resolved the interplay between DANC and cell architecture. The energy shuttle between mitochondria and ATPases is well established. Yet, the contribution of DANC in energy transfer is less understood. This paper explores how structural changes affect energy transfer efficiency.

Purpose Of The Study:

The aim of this study is to clarify the energetic interactions between subcellular organelles in striated muscles. Specifically, it focuses on how phosphotransfer kinases and DANC contribute to energy supply. The researchers propose to examine how these mechanisms adapt during development and in disease states. Striated muscle cells require precise energy delivery to function properly. The study investigates how mitochondrial organization influences energy transfer. The researchers also seek to determine how structural disorganization affects DANC efficiency. This work addresses the uncertainty in how energy systems respond to cellular remodeling. Understanding these interactions may shed light on energy deficiency in heart failure.

Main Methods:

The study uses a combination of biochemical assays and structural analysis to investigate energy transfer mechanisms. Researchers analyze the spatial organization of mitochondria and ATPases in striated muscle cells. They employ phosphotransfer kinase assays to measure energy shuttle efficiency. The study also includes developmental and disease models to observe changes in energy systems. Structural disorganization is induced to assess its impact on DANC and CK systems. The researchers use imaging techniques to map mitochondrial networks. They measure ATP and ADP transfer rates under different conditions. The study compares energy transfer mechanisms in healthy and diseased states.

Main Results:

The study found that phosphotransfer kinases and DANC both contribute to energy supply in striated muscles. DANC becomes more prominent when the CK system is inactivated. Mitochondrial networks are remodeled during postnatal development alongside CK system maturation. Structural disorganization reduces DANC efficiency and mitochondrial mass. In heart failure, both CK and DANC systems are impaired, contributing to energy deficiency. The researchers observed a decrease in DANC efficacy with cellular disorganization. ATP/ADP transfer rates correlate with mitochondrial proximity to ATPases. The study shows that energy transfer mechanisms are highly plastic and adaptable.

Conclusions:

The authors propose that energy transfer in striated muscles involves both phosphotransfer kinases and DANC. Structural changes in the cell significantly affect the efficiency of these systems. The study shows that DANC compensates when the CK system is impaired. Mitochondrial organization is crucial for efficient energy transfer. Disorganization in heart failure reduces DANC efficacy and contributes to contractile failure. The findings suggest that energy systems are tightly linked to cell architecture. The researchers conclude that both CK and DANC systems are essential for maintaining energy supply. These mechanisms are highly adaptable and respond to developmental and pathological changes.

Keywords:

cardiac muscle creatine kinase energy metabolism mitochondria organelle interaction sarcoplasmic reticulum skeletal muscle cells direct adenine nucleotide channeling striated muscle bioenergetics mitochondrial organization energy shuttle mechanisms cardiac muscle function

Frequently Asked Questions

The main mechanisms are phosphotransfer kinases like creatine kinase (CK) and direct adenine nucleotide channeling (DANC).

DANC directly channels ATP/ADP between mitochondria and ATPases, while CK shuttles energy via phosphotransfer reactions.

Mitochondrial proximity enables efficient ATP/ADP transfer, which is essential for DANC to function effectively.

DANC becomes more prominent as the CK system is inactivated, compensating for the loss in energy transfer efficiency.

Heart failure causes structural disorganization and reduced mitochondrial mass, decreasing DANC and CK system efficacy.

The researchers propose that impaired DANC contributes to energy deficiency and contractile failure in heart failure.

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