bims-mecosi 2021-10-03 papers

Issue of 2021‒10‒03
six papers selected by
Verena Kohler

Cells. 2021 Aug 25. pii: 2195. [Epub ahead of print]10(9):

Communications between Mitochondria and Endoplasmic Reticulum in the Regulation of Metabolic Homeostasis.

Pengcheng Zhang, Daniels Konja, Yiwei Zhang, Yu Wang.

Mitochondria associated membranes (MAM), which are the contact sites between endoplasmic reticulum (ER) and mitochondria, have emerged as an important hub for signaling molecules to integrate the cellular and organelle homeostasis, thus facilitating the adaptation of energy metabolism to nutrient status. This review explores the dynamic structural and functional features of the MAM and summarizes the various abnormalities leading to the impaired insulin sensitivity and metabolic diseases.

Keywords: MAM; endoplasmic reticulum; energy metabolism; mitochondria

DOI: https://doi.org/10.3390/cells10092195

Front Cell Dev Biol. 2021 ;9 726261

Lipid Droplet-Organelle Contact Sites as Hubs for Fatty Acid Metabolism, Trafficking, and Metabolic Channeling.

Mike F Renne, Hanaa Hariri.

Cells prepare for fluctuations in nutrient availability by storing energy in the form of neutral lipids in organelles called Lipid Droplets (LDs). Upon starvation, fatty acids (FAs) released from LDs are trafficked to different cellular compartments to be utilized for membrane biogenesis or as a source of energy. Despite the biochemical pathways being known in detail, the spatio-temporal regulation of FA synthesis, storage, release, and breakdown is not completely understood. Recent studies suggest that FA trafficking and metabolism are facilitated by inter-organelle contact sites that form between LDs and other cellular compartments such as the Endoplasmic Reticulum (ER), mitochondria, peroxisomes, and lysosomes. LD-LD contact sites are also sites where FAs are transferred in a directional manner to support LD growth and expansion. As the storage site of neutral lipids, LDs play a central role in FA homeostasis. In this mini review, we highlight the role of LD contact sites with other organelles in FA trafficking, channeling, and metabolism and discuss the implications for these pathways on cellular lipid and energy homeostasis.

Keywords: contact sites; fatty acids; lipid droplets; metabolism; organelles

DOI: https://doi.org/10.3389/fcell.2021.726261

Cells. 2021 Sep 01. pii: 2273. [Epub ahead of print]10(9):

Perspectives on Mitochondria-ER and Mitochondria-Lipid Droplet Contact in Hepatocytes and Hepatic Lipid Metabolism.

Xiaowen Ma, Hui Qian, Allen Chen, Hong-Min Ni, Wen-Xing Ding.

Emerging evidence suggests that mitochondrion-endoplasmic reticulum (ER) and mitochondrion-lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion-ER and mitochondrion-LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion-LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.

Keywords: NAFLD; alcohol; autophagy; lipophagy; lipotoxicity; starvation; steatosis

DOI: https://doi.org/10.3390/cells10092273

Cells. 2021 Sep 07. pii: 2341. [Epub ahead of print]10(9):

Intertwined and Finely Balanced: Endoplasmic Reticulum Morphology, Dynamics, Function, and Diseases.

Hannah T Perkins, Viki Allan.

The endoplasmic reticulum (ER) is an organelle that is responsible for many essential subcellular processes. Interconnected narrow tubules at the periphery and thicker sheet-like regions in the perinuclear region are linked to the nuclear envelope. It is becoming apparent that the complex morphology and dynamics of the ER are linked to its function. Mutations in the proteins involved in regulating ER structure and movement are implicated in many diseases including neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). The ER is also hijacked by pathogens to promote their replication. Bacteria such as Legionella pneumophila and Chlamydia trachomatis, as well as the Zika virus, bind to ER morphology and dynamics-regulating proteins to exploit the functions of the ER to their advantage. This review covers our understanding of ER morphology, including the functional subdomains and membrane contact sites that the organelle forms. We also focus on ER dynamics and the current efforts to quantify ER motion and discuss the diseases related to ER morphology and dynamics.

Keywords: anomalous diffusion; dynamics; dynein; endoplasmic reticulum (ER); kinesin; membrane contact site (MCS); microtubule; morphology

DOI: https://doi.org/10.3390/cells10092341

Cells. 2021 Sep 13. pii: 2408. [Epub ahead of print]10(9):

Role of ERLINs in the Control of Cell Fate through Lipid Rafts.

Valeria Manganelli, Agostina Longo, Vincenzo Mattei, Serena Recalchi, Gloria Riitano, Daniela Caissutti, Antonella Capozzi, Maurizio Sorice, Roberta Misasi, Tina Garofalo.

ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They are generally localized in the endoplasmic reticulum (ER), where ERLIN1 forms a heteroligomeric complex with its closely related ERLIN2. Well-defined functions of ERLINS are promotion of ER-associated protein degradation, mediation of inositol 1,4,5-trisphosphate (IP3) receptors, processing and regulation of lipid metabolism. Until now, ERLINs have been exclusively considered protein markers of ER lipid raft-like microdomains. However, under pathophysiological conditions, they have been described within mitochondria-associated endoplasmic reticulum membranes (MAMs), tethering sites between ER and mitochondria, characterized by the presence of specialized raft-like subdomains enriched in cholesterol and gangliosides, which play a key role in the membrane scrambling and function. In this context, it is emerging that ER lipid raft-like microdomains proteins, i.e., ERLINs, may drive mitochondria-ER crosstalk under both physiological and pathological conditions by association with MAMs, regulating the two main processes underlined, survival and death. In this review, we describe the role of ERLINs in determining cell fate by controlling the "interchange" between apoptosis and autophagy pathways, considering that their alteration has a significant impact on the pathogenesis of several human diseases.

Keywords: ERLINs; MAMs; apoptosis; autophagy; lipid rafts

DOI: https://doi.org/10.3390/cells10092408

Mol Biol Cell. 2021 Oct 01. 32(20): 1110

Preprint Highlight: ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA- dependent STING signaling.

Luis Bonet-Ponce.

Loss-of-function mutations in VPS13C cause familial Parkinson's disease (PD) and increase the risk to develop the sporadic form of the disease. However, the underlying disease mechanisms remain unclear. It has been previously established that VPS13C tethers lysosomes with the endoplasmic reticulum (ER) and promotes lipid interchange between both organelles. This study provides a cellular role of VPS13C, specifically regulating the cGAS/STING pathway and contributing to the innate immune response. The authors generate VPS13C knockout HeLa cells and use confocal microscopy and biochemical approaches to show loss of VPS13C leads to altered lysosome lipid composition and mitochondrial DNA leakage. Understanding how VPS13C preserves cellular homeostasis is an exciting discovery for scientists working on neurodegeneration and for cell biologists interested in lysosome-to-mitochondria cross-talk.

DOI: https://doi.org/10.1091/mbc.E21-10-0125p