Mother Brain

Mother Brain is a large, biological computer resembling a cycloptic, spiked brain and the leader of the Space Pirates. Since her debut in Metroid, Mother Brain has appeared as an antagonist, in various Metroid titles, often as the main one, and is the main antagonist of Captain N: The Game Master.

Captain N: The Game Master
Mother Brain was given a face and voice for her appearance in the animated television series, Captain N: The Game Master. She was the primary antagonist of the series, with various villains working under her. She was portrayed by acclaimed soul musician, Levi Stubbs.

Nintendo Comics System
In the Nintendo Comics System story "Duh Stoopid Bomb!", the name "M. Brain" can be seen on Wooster's list of people who think the Mushroom King is dumb. She also reprises her role as the main antagonist to Captain N in the Captain N: The Game Master series of comics.

Super Mario RPG: Legend of the Seven Stars
Mother Brain is briefly mentioned by Samus in Super Mario RPG: Legend of the Seven Stars, who claims to be "resting up for Mother Brain" at the Rose Town Inn.

WarioWare, Inc.: Mega Microgame$!
In WarioWare, Inc.: Mega Microgame$!, Mother Brain appears in the microgame Metroid, a recreation of the final boss of the original Metroid. To win the microgame, Samus must blast Mother Brain repeatedly with missiles while dodging her attacks to defeat her.

Super Smash Bros. for Nintendo 3DS / Wii U
Mother Brain appears as an Assist Trophy in Super Smash Bros. for Nintendo 3DS / Wii U. When she first appears, several Rinkas appear that damage opponents, and since they are energy-based, Rinkas can be absorbed or reflected. After some time, Mother Brain then uses the Laser Brain Attack for massive damage. When she uses the attack, however, the glass surrounding her container shatters, allowing opponents to attack and defeat her.

Super Smash Bros. Ultimate
Mother Brain returns as an Assist Trophy in Super Smash Bros. Ultimate, having no difference in behavior. She is also featured as a spirit.

Trivia

 * In the Brinstar stage seen in many Super Smash Bros. games, a massive brain can be seen occupying the background, writhing and occasionally sprouting wound-like growths whenever it comes in contact with the acid. Brinstar Depths contains another brain, this one smaller and trapped within a spherical spiked cage. It is unclear if either of these are intended to represent Mother Brain, though they do not particularly resemble any form of hers from the Metroid franchise.