Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes

Kumazawa, Azumi; Katoh, Hideki; Nonaka, Daishi; Watanabe, Tomoyuki; Saotome, Masao; Urushida, Tsuyoshi; Satoh, Hiroshi; Hayashi, Hideharu

doi:10.1253/circj.cj-13-1298

Cited by 19 publications

(16 citation statements)

References 32 publications

(27 reference statements)

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“…Tubulin tethering to mitochondria has been shown to play both structural and functional roles in striated muscle homeostasis [66] and disease [10]. Specifically, by physically and chemically interacting with the mitochondrial outer membrane, tubulin modulates the function of the permeability transition pore [67] and of voltage-dependent anion channels [68]. Mitochondrial tethering to cytoskeletal proteins involved in mechanosensing represents a mechanism through which the extracellular matrix may affect the contractile and metabolic apparatuses.…”

Section: Intracellular Energetic Units In Healthy Heartsmentioning

confidence: 99%

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains

Pasqualini

Nesmith

Horton

et al. 2016

BioMed Research International

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Efficient contractions of the left ventricle are ensured by the continuous transfer of adenosine triphosphate (ATP) from energy production sites, the mitochondria, to energy utilization sites, such as ionic pumps and the force-generating sarcomeres. To minimize the impact of intracellular ATP trafficking, sarcomeres and mitochondria are closely packed together and in proximity with other ultrastructures involved in excitation-contraction coupling, such as t-tubules and sarcoplasmic reticulum junctions. This complex microdomain has been referred to as the intracellular energetic unit. Here, we review the literature in support of the notion that cardiac homeostasis and disease are emergent properties of the hierarchical organization of these units. Specifically, we will focus on pathological alterations of this microdomain that result in cardiac diseases through energy imbalance and posttranslational modifications of the cytoskeletal proteins involved in mechanosensing and transduction.

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Section: Intracellular Energetic Units In Healthy Heartsmentioning

confidence: 99%

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains

Pasqualini

Nesmith

Horton

et al. 2016

BioMed Research International

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“…However, when isolated mitochondria are exposed to paclitaxel, no significant effects are detected; the authors suggested that paclitaxel does not promote MPT due to a direct effect on mitochondria [112]. However, it must be noted that lower concentrations were used in the latter study in comparison with previous work using liver mitochondria [110,112].…”

Section: Antimicrotubules -Taxanesmentioning

confidence: 82%

“…The cardiotoxicity promoted by paclitaxel is usually represented by subclinical sinus bradycardia (approximately 30 % of patients), but more severe conditions were also reported [3]. A recent study suggests that microtubule disorganization in cardiac myocytes promoted by paclitaxel leads to MTP pore opening [112]. However, when isolated mitochondria are exposed to paclitaxel, no significant effects are detected; the authors suggested that paclitaxel does not promote MPT due to a direct effect on mitochondria [112].…”

Section: Antimicrotubules -Taxanesmentioning

confidence: 99%

Mitochondrial Dysfunction on the Toxic Effects of Anticancer Agents— From Lab Bench to Bedside

Ribeiro¹,

eSantos²,

Custódio³

2015

Toxicology Studies - Cells, Drugs and Environment

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“…The absence of MACF1 could contribute to the release of DNM2 clustered on stable microtubule and consequently trigger mitochondria fission in mutant mice ( Macf1 f/f Cre+) (Kraus and Ryan, 2017). Alternatively, increase in microtubule dynamic instability directly impact local concentration of free tubulin (Gache et al, 2005) whereas free available tubulin-βII was shown to affect mitochondrial metabolism and organization (Kumazawa et al, 2014; Guzun et al, 2011; Guerrero et al, 2009). In this perspective, MACF1 could command mitochondria shape and functionality through the control of microtubule dynamics in muscle fibers.…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle MACF1 maintains myonuclei and mitochondria localization through microtubules to control muscle functionalities

Ghasemizadeh

Christin

Guiraud

et al. 2019

Preprint

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Skeletal muscle is made from multinuclear myofiber, where myonuclei are positioned at the periphery or clustered below neuromuscular junctions (NMJs). While mispositioned myonuclei are the hallmark of numerous muscular diseases, the molecular machinery maintaining myonuclei positioning in mature muscle is still unknown. Here, we identified microtubule-associated protein MACF1 as an evolutionary conserved regulator of myonuclei positioning, in vitro and in vivo, controlling the “microtubule code” and stabilizing the microtubule dynamics during myofibers maturation, preferentially at NMJs. Specifically, MACF1 governs myonuclei motion, mitochondria positioning and structure and acetylcholine receptors (AChRs) clustering. Macf1-KO in young and adult mice decreases muscle excitability and causes evolutionary myonuclei positioning alterations in adult mice, paralleled with high mitochondria content and improved resistance to fatigue. We present MACF1 as a primary actor of the maintenance of synaptic myonuclei and AChRs clustering, peripheral myonuclei positioning and mitochondria organization through the control of microtubule network dynamics in muscle fibers.

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Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes

Cited by 19 publications

References 32 publications

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains

Mitochondrial Dysfunction on the Toxic Effects of Anticancer Agents— From Lab Bench to Bedside

Skeletal muscle MACF1 maintains myonuclei and mitochondria localization through microtubules to control muscle functionalities

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