Module 8.2 - Nanotubules, Exosomes, MAMs

57 Questions

Movement between and within cells, and membrane dynamics are essential parts of efficient metabolism in ______

cells

When we think of what causes metabolic disease, we often do not focus on cellular ______

trafficking

Understanding these basic processes in cells will help us work out what underlies complex ______

disease

Once you have phosphoAKT, you will break ER-mitochondria interaction, and Calcium influx into mitochondria will stop because you don’t need the energy production ______

anymore

It has been understudied because we lacked high resolution tools to study these processes (in vivo is exponentially ______)

harder.

PAPER TO READ FOR NEXT ______

CLASS

Exosomes are lipid-rich vesicles that carry ______ and proteins

RNA

Exosomes play a crucial role in the heart's response to stress, as they carry glucose transporters and enzymes to promote glucose uptake and metabolism in ______ cells

endothelial

Neurons can transfer mitochondria through ______, aiding in energy transmission and potentially offering a therapeutic approach for neurological diseases

nanotubules

Mitochondria, the cell's ______, can communicate through nanotunnels, exchanging ions, metabolites, and nucleic acids, especially in cells with limited mitochondrial movement

powerhouses

Mitochondrial nanotunnels may act as sensing probes for the intracellular environment, potentially aiding in the response to ______ signals and the transfer of healthy mitochondria

harmful

Mitochondria contain 2-10 copies of ______, and maintaining a healthy ratio of good to bad mtDNA is crucial for cell function and disease prevention

mtDNA

The signaling and communication within MAMs are a complex and active process, with implications for various cellular functions, making it a crucial area for further ______

research

Exosomes are rapidly taken up by other ______ (e.g. liver, lung and spleen) mRNA signals travels to other cells to give them signals, these are usually inhibitory signals for shutting down translation in other cells internalization

tissues

______ -tiny secretory vesicles, don’t quite understand how budding happens Extracellular vesicles (EVs) of 50 – 150 nm is size (larger ones have other names) Believed to be generated from the MVB (multivesicular body) RNAs and miRNAs appear to be selectively sorted into exosomes Cargo is protected from degradation while in the circulation

Exosomes

Exosomes: An alternative way for cells to communicate Cargo: miRNAs, lncRNA, circRNA (nucleic acids) – genomic ‘signals’ Proteins – cytosolic, intracellular signals that are not traditionally secreted Membrane-bound proteins (e.g.

Cells

Exosomes as new players in metabolic organ cross-talk. DOM. 2017. fusion

Metabolic

Roles for ______ Trafficking in Metabolic Diseases Obesity Dr. Jennifer Estall Diabetes @dnachicken IRCM, Montréal [email protected] Outline of Lecture Lecture 2: Exosomes Nanotubes and Nanotubules Mitochondrial associated membranes (MAMs) What they are and why are they important to metabolism and disease Cell – cell communication beyond secreted proteins What does this mean for the field of metabolism.

Cellular

What they are and why are they important to metabolism and disease Cell – cell communication beyond secreted proteins

Metabolism

______ – cytosolic, intracellular signals that are not traditionally secreted Membrane-bound proteins (e.g.

Proteins

Isolation of involves using a sucrose gradient to separate them from other membranes, and this method has been used to successfully isolate .

MAMs

MAMs contain a unique set of , including ER , Mito , and unique , making them very different from normal mitochondria.

proteins

MAMs are enriched in proteins necessary for ion transport and cell ______, including those involved in calcium transport, apoptosis, and metabolism.

signaling

MAMs permit Ca+2 flow into mitochondria, acting as a direct door for calcium when it is needed, and creating ______ of second messenger signals.

microdomains

MAMs are dynamic and move/reorient in response to cell signaling, and the interaction is tightly regulated by ______ for calcium-induced signaling molecules.

receptors

MAMs play a role in skeletal muscle contraction, heart contraction, insulin secretion, and liver , and their interactions might help regulate in the fasted versus fed state.

metabolism

The study of MAMs involves understanding their unique ______ and protein composition, their role in metabolism and cell signaling, and their dynamic nature in response to cellular needs.

lipid

What is a feature of many metabolic diseases?

Decreased ER-mitochondrial targets

What is the role of MAMs in cellular function?

Aiding in energy transmission

What is a potential therapeutic approach for neurological diseases?

Transfer of mitochondria through nanotunnels

What do exosomes carry for promoting glucose uptake and metabolism in cells?

Proteins

What is a characteristic of exosomes?

Released into the extracellular space

What is the consequence of having phosphoAKT?

Decreased energy production

What is a crucial area for further study in cellular metabolism?

Mitochondrial nanotunnels

What is a role of mitochondrial nanotunnels?

Exchange of ions and metabolites

What is a potential consequence of altered MAM structure and function?

Dysregulated energy metabolism

What is the role of exosomes in the heart's response to stress?

Carrying glucose transporters and enzymes to promote glucose uptake and metabolism in endothelial cells

What is the function of mitochondrial nanotunnels?

Acting as sensing probes for the intracellular environment and aiding in the response to harmful signals

What is the significance of maintaining a healthy ratio of good to bad mtDNA in mitochondria?

Crucial for cell function and disease prevention

What are mitochondria-associated membranes (MAMs) defined by?

Direct contact with mitochondria, higher lipid concentration, unique lipid and protein profile facilitating signaling and tethering

What is the role of ER-mitochondrial interactions in MAMs?

Significant role in unique signaling, lipid synthesis, and protein folding

What is the function of exosomes in inter-cellular communication?

Carrying RNA and proteins to influence gene transcription in other cell types

What can neurons transfer through nanotubules, aiding in energy transmission and potentially offering a therapeutic approach for neurological diseases?

Mitochondria

What are exosomes?

Tiny secretory vesicles, believed to be generated from the multivesicular body (MVB), containing RNAs, miRNAs, and proteins

What is the role of mitochondrial associated membranes (MAMs) in cell function?

MAMs permit Ca$^{2+}$ flow into mitochondria, acting as a direct door for calcium when it is needed, and creating a hub of second messenger signals

What is the cargo of exosomes?

miRNAs, lncRNA, circRNA (nucleic acids) and proteins

What is the proposed role of MAMs in metabolism?

Serving as a reservoir for specific lipid species, site of lipid metabolism, and mediating autophagy

What is the function of exosomes in cell-cell communication?

Rapidly taken up by other tissues, carrying inhibitory signals for shutting down translation in other cells

What happens when specific lipids are depleted from MAMs?

MAM-associated proteins redistribute, leading to reorganization of the mitochondrial network and dissociation of MAMs

What is the significance of MAMs in metabolic diseases?

Altered MAM structure and function is a feature of many metabolic diseases

What is a characteristic of the protein composition of MAMs?

Contain ER proteins, Mito proteins, and unique proteins, making them very different from normal mitochondria

What is the role of MAMs in cellular signaling?

MAMs are enriched in proteins necessary for ion transport and cell apoptosis, and are involved in calcium signaling and metabolism

What is the function of MAMs in regulating cellular processes?

Bringing calcium to mitochondria when needed and turning off the system when it is not

What is the content of exosomes?

Nucleic acids (miRNAs, lncRNA, circRNA) and proteins

How are MAMs involved in cell signaling?

Creating microdomains of second messenger signals

What is the significance of MAMs in the transition from fasting to feeding?

Regulating metabolism and insulin secretion

What is a key characteristic of the dynamic nature of MAMs?

They move/reorient in response to cell signaling and their interaction is tightly regulated by receptors for calcium-induced signaling molecules

Study Notes

Studying Mitochondrial-Associated ER Membranes (MAMs)

Isolation of MAMs involves using a sucrose gradient to separate them from other membranes, and this method has been used to successfully isolate MAMs.
MAMs contain a unique signature of lipids, including enrichment with cholesterol and ceramides, which allows them to be isolated and dissolved without problems.
Depletion of specific lipids causes MAM-associated proteins to redistribute, leading to reorganization of the mitochondrial network and dissociation of MAMs.
MAMs contain a unique set of proteins, including ER proteins, Mito proteins, and unique proteins, making them very different from normal mitochondria.
MAMs are enriched in proteins necessary for ion transport and cell signaling, including those involved in calcium transport, apoptosis, and metabolism.
Proposed roles of MAMs in metabolism include serving as a reservoir for specific lipid species, site of lipid metabolism, and mediating autophagy.
MAMs permit Ca+2 flow into mitochondria, acting as a direct door for calcium when it is needed, and creating microdomains of second messenger signals.
MAMs are dynamic and move/reorient in response to cell signaling, and the interaction is tightly regulated by receptors for calcium-induced signaling molecules.
MAMs play a role in skeletal muscle contraction, heart contraction, insulin secretion, and liver metabolism, and their interactions might help regulate metabolism in the fasted versus fed state.
Mito/ER interactions might help regulate metabolism in the transition from fasting to feeding, where glucagon promotes the connection of ER to mito, and insulin secretion is linked to MAMs.
MAMs are involved in bringing calcium to mitochondria when it is needed and turning off the system when it is not, making them vital for various cellular processes.
The study of MAMs involves understanding their unique lipid and protein composition, their role in metabolism and cell signaling, and their dynamic nature in response to cellular needs.