bims-mecosi 2023-02-19 papers

Issue of 2023‒02‒19
three papers selected by
Verena Kohler

Front Cardiovasc Med. 2023 ;10 1083935

Mitochondria-associated endoplasmic reticulum membranes (MAMs): Possible therapeutic targets in heart failure.

Yu Zhang, Jiayu Yao, Mingming Zhang, Yushan Wang, Xingjuan Shi.

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are formed by physical connections of the endoplasmic reticulum and mitochondria. Over the past decades, great breakthroughs have been made in the study of ER-mitochondria communications. It has been identified that MAM compartments are pivotal in regulating neurological function. Accumulating studies indicated that MAMs participate in the development of cardiovascular diseases. However, the specific role of MAMs in heart failure remains to be fully understood. In this article, we first summarize the structural and functional properties of MAM and MAM-associated proteins. We then focus on the roles of MAMs in myocardial infarction, cardiomyopathy and heart failure, and discuss the involvement of MAMs in disease progression and treatment. Elucidating these issues may provide important insights into therapeutic intervention of heart failure.

Keywords: cardiomyopathy; cardiovascular diseases; heart failure; mitochondria-associated membranes (MAMs); myocardial infarction

DOI: https://doi.org/10.3389/fcvm.2023.1083935

Exp Cell Res. 2023 Feb 10. pii: S0014-4827(23)00059-9. [Epub ahead of print] 113512

Mitochondria-associated endoplasmic reticulum membranes promote mitochondrial fission through AKAP1-Drp1 pathway in podocytes under high glucose conditions.

Xuehong Li, Qinglan Yang, Sirui Liu, Shicong Song, Cheng Wang.

Excessive mitochondrial fission in podocytes is a critical feature of diabetic nephropathy (DN). Mitochondria-associated endoplasmic reticulum membranes (MAMs) are contact sites between the endoplasmic reticulum (ER) and mitochondria, which are suggested to be related to mitochondrial function. However, the role of MAMs in mitochondrial dynamics disorder in podocytes remains unknown. Here, we firstly reported a novel mechanism of MAMs' effects on mitochondrial dynamics in podocytes under diabetic conditions. Increased MAMs were found in diabetic podocytes in vivo and in vitro, which were positively correlated with excessive mitochondrial fission. What's more, we also found that A-kinase anchoring protein 1 (AKAP1) was located in MAMs, and its translocation to MAMs was increased in podocytes cultured with high glucose (HG). In addition, AKAP1 knockdown significantly reduced mitochondrial fission and attenuated high glucose induced-podocyte injury through regulating phosphorylation of dynamin-related protein 1 (Drp1) and its subsequent mitochondrial translocation. On the contrary, AKAP1 overexpression in these podocytes showed the opposite effect. Finally, pharmacological inhibition of Drp1 alleviated excessive mitochondrial fission and podocyte damage in AKAP1 overexpressed podocytes. Our data suggest that MAMs were increased in podocytes under diabetic conditions, leading to excessive mitochondrial fission and podocyte damage through AKAP1-Drp1 signaling.

Keywords: Diabetic nephropathy; MAM; Mitochondria; Podocyte

DOI: https://doi.org/10.1016/j.yexcr.2023.113512

Biophys J. 2023 Feb 10. pii: S0006-3495(22)03000-4. [Epub ahead of print]122(3S1): 379a-380a

Plasma membrane curvature promotes ER-PM contact formation mediated by junctophilin.

Yang Yang, Bianxiao Cui.

DOI: https://doi.org/10.1016/j.bpj.2022.11.2084