Visualizing Mitochondrial Form and Function within the Cell

Abstract

The specific cellular role of mitochondria is influenced by the surrounding environment because effective mitochondrial function requires the delivery of inputs (e.g., oxygen) and export of products (e.g., signaling molecules) to and from other cellular components, respectively. Recent technological developments in mitochondrial imaging have led to a more precise and comprehensive understanding of the spatial relationships governing the function of this complex organelle, opening a new era of mitochondrial research. Here, I highlight current imaging approaches for visualizing mitochondrial form and function within complex cellular environments. Increasing clarity of mitochondrial behavior within cells will continue to lend mechanistic insights into the role of mitochondria under normal and pathological conditions and point to spatially regulated processes that can be targeted to improve cellular function.

Keywords: 3D electron microscopy; Energy metabolism; super-resolution microscopy; systems-level imaging.

Figure 1:. Mitochondrial function relies on cellular interactions.

Depiction of a mitochondrion within a cell highlighting some of the many interactions with other cellular structures that can regulate acute mitochondrial function. Mitochondrial inputs are listed next to arrows pointing toward the mitochondrion and mitochondrial products are listed next to arrows pointing away from the mitochondrion. Interactions involved in assembling and degrading mitochondria are not shown. Structures not drawn to scale.

Figure 2:. Recent advances in mitochondrial imaging.

A) Fluorescent antibody labeled mitochondria (magenta) and lysosomes (yellow) within two layer V pyramidal neurons of the mouse somatosensory cortex visualized by expansion lattice light sheet microscopy. Scale bars: 5μm (inset 10μm). B) Mitochondrial cristae structure within live HeLa cells expressing a Cox8a-SNAP fusion protein and labeled with SNAP-Cell SiR dye as imaged by a stimulated emission depletion super-resolution microscope. Scale bar: 1μm. C) 3D rendering of contacts between mouse skeletal muscle mitochondria (cyan), sarcoplasmic reticulum (magenta), and t-tubules (orange) visualized with focused ion beam scanning electron microscopy and machine learning organelle segmentation. Scale bar: 1μm. D) Dynamic interactions between genetically-encoded mitochondria (mEmerald-Tomm20, green), lysosomes (HaloTag-Lamp1, magenta), and microtubules (mCherry-ensconsin, yellow) in COS-7 cells visualized on a grazing incidence structured illumination microscope. Scale bar: 1μm. Reproduced with permission from [23], [36], [2], [40], respectively.