Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation

Cattin, Marie-Elodie; Wang, Jessica; Weldrick, Jonathan J.; Roeske, Cassandra; Mak, Esther; Thorn, Stephanie; DaSilva, Jean N.; Wang, Yibin; Lusis, AJ; Burgon, Patrick G.

doi:10.1074/jbc.m115.678433

Cited by 28 publications

(61 citation statements)

References 49 publications

(53 reference statements)

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“…IGF-I may only produce a trade-off between current benefits to reproduction and later costs in senescence, like the relationship between inotropic agents and exacerbation of heart failure 168 . Interestingly, activation of Akt weakens cardiac adaptation to stress 169 and exacerbates the aging phenotype in the heart, effects which are accompanied by suppression of autophagy 170 . However, the specific role of Akt in cardiac aging and how autophagy affects this process are not yet known.…”

Section: Relevant Intracellular Signaling Mechanisms Controlling Amentioning

confidence: 99%

Aging and Autophagy in the Heart

Shirakabe

Ikeda

Sciarretta

et al. 2016

Circulation Research

365

273

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The aging population is increasing in developed countries. Since the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypertrophy, fibrosis, and accumulation of misfolded proteins and dysfunctional mitochondria. Macroautophagy (hereafter referred to as “autophagy”) is a lysosome-dependent bulk degradation mechanism that is essential for intracellular protein and organelle quality control. Autophagy and autophagic flux are generally decreased in aging hearts, and murine autophagy loss-of-function models develop exacerbated cardiac dysfunction that is accompanied by accumulation of misfolded proteins and dysfunctional organelles. On the other hand, stimulation of autophagy generally improves cardiac function in mouse models of protein aggregation by removing accumulated misfolded proteins, dysfunctional mitochondria, and damaged DNA, thereby improving the overall cellular environment and alleviating aging-associated pathology in the heart. Increasing lines of evidence suggest that autophagy is required for many mechanisms that mediate lifespan extension, such as caloric restriction, in various organisms. These results raise the exciting possibility that autophagy may play an important role in combating the adverse effects of aging in the heart. In this review, we discuss the role of autophagy in the heart during aging, how autophagy alleviates age-dependent changes in the heart, and how the level of autophagy in the aging heart can be restored.

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Section: Relevant Intracellular Signaling Mechanisms Controlling Amentioning

confidence: 99%

Aging and Autophagy in the Heart

Shirakabe

Ikeda

Sciarretta

et al. 2016

Circulation Research

365

273

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“…Muscle-enriched A-type lamin-interacting protein (Mlip) 3 is encoded by a unique gene that is conserved among amniotes. Mlip was initially discovered through its interaction with A-type lamins (1) and with transcription factor ISL1 (2).…”

Section: Rapid Amplification Of Cdna Ends (Race) Of Mlip Transcripts mentioning

confidence: 99%

“…The Mlip gene is most abundantly expressed in the heart and skeletal muscles with lower expression levels of Mlip also detected in other tissues (e.g. liver and brain) in both mouse and human (1,3). Mlip is expressed in both the cytosol and nucleus of cells and colocalizes with A-type lamin and promyelocytic leukemia bodies in the nucleus (1).…”

Section: Rapid Amplification Of Cdna Ends (Race) Of Mlip Transcripts mentioning

confidence: 99%

“…Mlip is expressed in both the cytosol and nucleus of cells and colocalizes with A-type lamin and promyelocytic leukemia bodies in the nucleus (1). Despite recent studies that demonstrated that Mlip plays a crucial role in cardiac homeostasis and adaptation in response to stress (3)(4)(5), the exact molecular functions of MLIP remain unknown.…”

Section: Rapid Amplification Of Cdna Ends (Race) Of Mlip Transcripts mentioning

confidence: 99%

“…The investigation of MLIP's molecular function is complicated by the complex nature of the proteins: Mlip mRNA is alternatively spliced and gives rise to at least seven different mature mRNA and protein isoforms in the heart (1,3). The splicing patterns and expression profile have not yet been characterized in the other tissues, but the pattern of MLIP isoform expression appears to be dependent on tissue type.…”

Section: Rapid Amplification Of Cdna Ends (Race) Of Mlip Transcripts mentioning

confidence: 99%

See 2 more Smart Citations

Expression of murine muscle-enriched A-type lamin-interacting protein (MLIP) is regulated by tissue-specific alternative transcription start sites

Cattin

Deeke

Dick

et al. 2018

Journal of Biological Chemistry

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How cardiomyocytes sense pathophysiological stresses for cardiac remodeling

Haque

Wang

2016

Cell. Mol. Life Sci.

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In the past decades, the cardiovascular community has laid out the fundamental signaling cascades that become awry in the cardiomyocyte during the process of pathologic cardiac remodeling. These pathways are initiated at the cell membrane and work their way to the nucleus to mediate gene expression. Complexity is multiplied as the cardiomyocyte is subjected to cross talk with other cells as well as a barrage of extracellular stimuli and mechanical stresses. In this review, we summarize the signaling cascades that play key roles in cardiac function and then we proceed to describe emerging concepts of how the cardiomyocyte senses the mechanical and environmental stimuli to transition to the deleterious genetic program that defines pathologic cardiac remodeling. As a highlighting example of these processes, we illustrate the transition from a compensated hypertrophied myocardium to a decompensated failing myocardium, which is clinically manifested as decompensated heart failure.

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Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation

Cited by 28 publications

References 49 publications

Aging and Autophagy in the Heart

Aging and Autophagy in the Heart

Expression of murine muscle-enriched A-type lamin-interacting protein (MLIP) is regulated by tissue-specific alternative transcription start sites

How cardiomyocytes sense pathophysiological stresses for cardiac remodeling

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