The Canadian-American comedy star, who won her second career Emmy, for Lead Actress, in Schitt's Creek in 2020, was 71.
She died on Friday at her home in Los Angeles "following a brief illness," her agency, Creative Artists Agency (CAA), said in a statement. No further details were available.
In an entertainment career spanning more than 50 years, she also appeared in several hit comedy movies, including Beetlejuice and its sequel, and gave a memorable turn as Kate McCallister, Macaulay Culkin's stressed mother in the first two Home Alone films.
Culkin, who starred as the youngster accidentally left at home when his family leaves for a Christmas holiday in the 1990 classic, posted a heartfelt tribute on Instagram, calling her "Mama" and saying he thought they "had time".
The pair reprised their roles in the 1992 sequel, Home Alone 2: Lost In New York.
Meryl Streep, who co-starred with O'Hara in the 1986 comedy drama, Heartburn, said in a statement that O'Hara "brought love and light to our world, through whipsmart compassion for the collection of eccentrics she portrayed".
O'Hara frequently collaborated with mockumentary pioneer Christopher Guest, becoming a key player in his ensemble and starring in Waiting for Guffman, Best in Show and A Mighty Wind.
Her popularity surged after the success of Schitt's Creek, which dominated the 2021 Emmys following its sixth and final season, bringing O'Hara a new generation of fans.
She enjoyed a late career renaissance that led to a serious role in HBO's post-apocalypse drama, The Last Of Us, for which she was nominated for an Emmy.
Pedro Pascal, her costar, said on Instagram: "There is less light in my world, this lucky world that had you".
She was also nominated for an Emmy for her performance as Hollywood producer Patty Leigh in the Seth Rogen Hollywood satire, The Studio, which also earned her a Golden Globe nomination.
O'Hara's career was launched at the Second City Theatre in Toronto, where she was born, in the 1970s.
It was there that she first worked with Eugene Levy, who would become a lifelong collaborator - and her Schitt's Creek costar.
While at Second City, she helped create the sketch comedy show SCTV - in which both she and Levy appeared - and which helped launch the careers of other top Canadian comedians, including John Candy, Andrea Martin, Rick Moranis and Martin Short.
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She is survived by her husband, Bo Welch, and sons Matthew and Luke and her family will hold a private celebration of her life, the CAA statement said.
The charges include conspiracy and interfering with the First Amendment rights of worshippers.
The 59-year-old was one of four people detained in connection with the protest inside Cities Church in St Paul during a service on 18 January.
Lemon livestreamed the demonstration, which took place because activists alleged that a pastor associated with the church also held a leadership role within Immigration and Customs Enforcement (ICE).
Lemon has maintained he was observing the protest as a reporter.
US attorney general Pam Bondi confirmed the arrests on social media on Friday.
She wrote: "At my direction, early this morning federal agents arrested Don Lemon, Trahern Jeen Crews, Georgia Fort, and Jamael Lydell Lundy, in connection with the coordinated attack on Cities Church in St. Paul, Minnesota.
"More details soon."
Abbe Lowell, Lemon's attorney, called the arrest an "unprecedented attack on the First Amendment" - which includes freedom of the press - and said his client will "fight these charges vigorously and thoroughly in court".
Mr Lowell said: "Don has been a journalist for 30 years, and his constitutionally protected work in Minneapolis was no different than what he has always done.
"Instead of investigating the federal agents who killed two peaceful Minnesota protesters, the Trump Justice Department is devoting its time, attention and resources to this arrest, and that is the real indictment of wrongdoing in this case.
"This unprecedented attack on the First Amendment and transparent attempt to distract attention from the many crises facing this administration will not stand."
Mr Lowell said Lemon had been in Los Angeles covering the upcoming Grammy Awards at the time of his arrest.
In a statement, CNN also criticised the arrest of their former presenter, and said it "raises profoundly concerning questions about press freedom".
It comes as US deputy attorney general Todd Blanche confirmed the DoJ had opened a federal investigation into a potential civil rights violation regarding the killing of Alex Pretti, who was shot and killed by border control agents last Saturday.
Mr Blanche said: "We're looking at everything that would shed light on that day."
The killing of the 37-year-old ICU nurse came weeks after Renee Good was shot dead in her car, less than a mile from where Mr Pretti was fatally shot.
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Homeland Security spokesperson Tricia McLaughlin said earlier this week that two agents who fired their guns during Mr Pretti's shooting have been placed on administrative leave.
That has been the entire tenor of his three-day visit to China as the former human rights lawyer-turned prime minister seeks tor reset Britain's relationship with China.
Ask him about Donald Trump's warning that it's "very dangerous" for the UK to seek closer ties with China, and Starmer swerves.
Ask him about the plight of the pro-democracy campaigner Jimmy Lai, imprisoned in Hong Kong, and he says the issues has been raised, but he doesn't want to go into it.
Ask him whether he agrees with Mark Carney critique that the middle powers need to work together to counter the rise of great powers - the US and China, he distances.
He is, if you like, making pragmatic choices to find favour with the big beast nations - be it on Jimmy Lai, or the building of a super embassy for China, or allowing Trump to troll him on a variety of subjects according to his fancy. Starmer keeps his head down and ploughs on.
His supporters say this pragmatism delivers results, be it a better trade deal with the US, or the prospect of great investment and trade with the world's second-biggest economy China.
His detractors argue that the UK is supine and the prime minister is leaving his country to the mercy of much bigger powers.
Canadian Prime Minister Mark Carney sees a third way.
"Great powers can afford, for now, to go it alone. They have the market size, the military capacity and the leverage to dictate terms. Middle powers do not. The middle powers must act together, because if we're not at the table, we're on the menu," he told the annual Davos summit earlier this month.
As Trump comes for Carney - his recent visit to China and narrow trade deals prompted Trump to threaten 100% tariffs - Starmer ducks for cover.
When I asked him in Shanghai whether he agreed with Carney's critique of the shifting global order, well he does not.
"I've talked to Mark Carney a lot, but we're living in a very volatile world.
"My compass is always the national interest of the United Kingdom, and I'm very clear that that means that we maintain and build on our close relationship with the US; that we build a stronger and closer relationship with Europe, but that we also are confident and engaging outwardly and that means with China."
"I take the view that it's in the UK's national interest to maintain our relationship with the US.
"It's close on defence, security, intelligence, actually on trade and prosperity as well.
"On Europe, I want to do more on defence and security and one trade. But on the outgoing world, I mean China as well. We need to be outward, engaging. And that's been the stance of the government since the beginning."
As Starmer tows a line, Trump is rattled by the behaviour of allies.
"I think its very dangerous for them to do that," he said when asked about the UK seeking closer ties with China.
But he reserved most of his ire for Canada: "It's even more dangerous, I think, for Canada to get into business with China. Canada is not doing well. They're doing very poorly, and you can't look at China as the answer."
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But the UK is looking to China as part of the answer as it deepens trade ties, and the three-day tour was an exercise in trying to put differences aside as Starmer seeks a reset that the UK needs more than Beijing.
Starmer comes away from China with sanctions on six parliamentarians, barred from visiting China for speaking out on human rights issues, lifted. There is a tariff cut on whiskey imports from 10% to 5%, and the deal in principle for visa-free travel for up to 30 days - a big win for business.
It is, the No 10 delegation says, "not a one-and-done trip", but the beginning of a deeper reset.
The prime minister told me that he hoped President Xi would visit in the UK in 2027 when it hosts the G20. It will be the first time in over 10 years that the Chinese leader has set foot on British soil.
But the reasons for freezing relations remain.
For all the warm handshakes and words, there are deep differences and areas of discomfort between Britain's democracy and China's autocracy.
Rifts between the two nations were in part caused in response to China's crackdown in Hong Kong.
The imprisonment of British pro-democracy campaigner Jimmy Lai remains a contentious issue. Keir Starmer says he raised the matter with President Xi.
When I asked if he specifically raised Lai's name, he said yes. But as for Lai's release, the PM said he wouldn't get into the deals.
"I am absolutely clear about, the raising, the manner in which we raised it and the importance of raising it. What you can't do is sit back at home with your head in the sand saying, I'm not going to talk to you…if you're just sitting outside the room, refuse to engage, you can't even have the conversation."
But there are plenty of opponents back home who disagree with the engagement.
Nusrat Ghani, one of the five MPs sanctioned in 2021, posted on X: "MPs agreed that the Chinese Communist Party was orchestrating a genocide against the Uyghur people. The sanctions were meant to intimidate us MPs and prevent us from doing our jobs without fear or favour. Bartering our MP sanctions doesn't change those facts nor help others in the UK targeted by CCP and sanctioned by them."
Kemi Badenoch, the Conservative leader, has also been highly critical, concerned about national security, the crackdown on political freedoms in Hong Kong and Chinese "undermining" of the UK economy - be it through cheap Chinese goods that undermine British manufacturing, overreliance on Chinese technology or Chinese influence in critical infrastructure.
So when the UK hailed a $15bn (£12bn) investment in AstraZeneca on the trip over, having paused a £200m investment at a Cambridge research site last September which was due to create 1,000 jobs, shadow business secretary Andrew Griffith was blunt in his assessment.
"AstraZeneca's a great British company but under this government it's investing everywhere in the world other than its UK home. When we are losing investment to communist China, alarm bells should be ringing in No 10 Downing Street."
Others ask what has he actually come back with? He has not secured the scale of trade deals struck by PM Carney, and I am told by one person in the UK delegation that after Britain's snub of President Xi, it will take some time to rebuild ties.
But for Starmer, the prize is deepening economic ties, more investment and trade.
For a British prime minister struggling to grow this economy, drumming up more business with the world's second largest economy - even if you don't much like its political system, or choice of allies such as Russia - can be chalked up as a win.
You can perhaps swallow some of that if you can agree, as Starmer did on Thursday, to launch a "feasibility study" on a bilateral services pact.
The UK had a £10bn surplus in services with China in the year to last June. It is a market ripe for growth.
For this former human rights lawyer turned self-avowed pragmatist, drumming up business will both take priority over obvious differences around human rights, espionage and China's continued support of Russia during the years of war in Ukraine.
Carney argues that middle powers need to push back the superpowers, but Starmer seems happy to try to comply. It matters less to him if he is at the mercy of the US or China, if it means he can help deliver back home.
The Chinese will next month welcome in the year of the horse in 2026, a creature which in their zodiac represents action, speed and breakthrough.
Starmer is going to need all of that in spades if he is to usher in a year that will cut the cost of living back home.
He will leave Shanghai with the hope that this visit might help - but it's going to require a lot more work, not just with Beijing, but with his other superpower too.
Estimates from human rights organisations and doctors, independent of the Iranian regime's official figures, range from over 5,000 at the conservative end to 33,000 by one count, and even as high as 50,000, according to one unverified claim.
Iranian authorities imposed a near-total internet blackout, which has only partially lifted, from 8 to 27 January. As a result, it has been near-impossible to verify the true number of people who have been killed in the brutal crackdown.
Nicholas Hopton, former UK ambassador to Iran from 2016 to 2018, told Sky News that Iranian authorities were limiting information on the number of people killed.
"It is becoming increasingly clear since the internet coverage has been partially restored in the last week, that many thousands, possibly tens of thousands of innocent people, were killed during the crackdown by the Islamic regime," he said.
The Iranian Islamic Republic previously said 3,117 people have been killed, claiming the majority of these deaths were security forces and civilians, not protesters. But this number has been questioned by doctors, diplomats and human rights organisations.
"One should view any statistics being given by the Iranian authorities with a big dose of scepticism," Mr Hopton added.
The UN's special rapporteur on Iran, Mai Soto, has said at least 5,000 people have been killed at a "minimum" - substantially more than the authorities' claims.
Human rights agencies also warn the numbers are much higher. The US-based Human Rights Activists News Agency (HRANA) has independently verified 6,540 deaths so far, with a further 17,091 cases under review, bringing the possible total up to over 23,500.
It said just 214 deaths verified so far have been government-affiliated, such as security forces, while the majority, 6,148, have been protesters, 123 were under 18 and 55 were civilians.
Doctors claim tens of thousands have been killed
Meanwhile, two doctors have told Sky News they believe tens of thousands of people have been killed.
Germany-based eye surgeon Dr Amir-Mobarez Parasta claimed major hospitals and clinics inside Iran have seen over 25,000 clinically recorded deaths as of 23 January.
Dr Parasta is a supporter of Reza Pahlavi, the son of the former shah of Iran, who lives in the US and is a prominent voice encouraging protests against the regime.
He said he had collected the figures from a network of doctors and medical professionals across Iran, and claimed they had been verified by at least two individuals in each hospital or clinic where the data was from.
Sky News has not seen the clinical reports he cited and is unable to independently verify the figure.
Dr Yaser Rahmani-Rad, a specialist in internal medicine at a Tehran hospital who was previously arrested in 2023 for treating protesters, also believes the number of people killed is in the tens of thousands. Some doctors have been arrested for treating protesters during this bout of unrest, Sky News previously reported.
High number of deaths recorded in capital
Of the deaths Dr Parasta claims have been clinically recorded, a third (8,354) were in Tehran alone. As the nation's capital and largest city, Tehran was a hotbed of protest activity and is widely considered to be the location of the first protests on 28 December.
Nearly 900 protests were identified between 28 December and 13 January, through research from Sky News and the Institute for the Study of War (ISW).
Dr Parasta's report estimates that with a lack of data from areas across Iran and around 15% of deaths likely being underreported at this stage, the true number of people who have died is likely higher - at least 33,130.
Former UN prosecutor and human rights lawyer Payam Akhavan told Sky News he believes that estimate is credible, though Dr Parasta said he considers his figure to be "conservative".
"Our ongoing data collection shows a continued and significant rise in hospital-reported deaths, reflecting both the sustained intensity of the violence and the severe strain on an already overwhelmed healthcare system," he said.
The son of the former shah of Iran, Reza Pahlavi, has said the figure could be as high as 50,000 dead, without providing evidence to support the claim.
A 'massacre' amid internet blackouts
On 8 January, observed protest activity reached its peak and the internet blackout began. Now, reports from doctors suggest the days which followed were the deadliest for protesters.
"The concentration and scale of fatalities during this period compel us to speak of a massacre-level event," Dr Parasta told Sky News.
Sky News has verified footage from several locations around Iran during this period, which appears to show security forces opening fire on protesters.
One picture posted on social media shows a machine gun mounted on top of a military vehicle in Tehran.
Mr Hopton, the former ambassador, said 8 and 9 January were particularly fatal.
Dr Rahmani-Rad, who is based in Tehran, said: "What happened in Iran over those two days is something the world has never seen with its own eyes.
"I still cannot believe that something like this actually happened. I still haven't fully accepted it."
Putting the numbers into perspective
Defining the number of those killed in previous protests in Iran is similarly contentious, with competing narratives from authorities and human rights organisations.
During the Iranian Revolution in 1979 - previously believed to be the most violent in Iran's history - it is estimated between 532 and 2,781 people died, according to military historian Spencer C Tucker, who has written several books on revolutions and the Middle East.
The Iranian regime has put this figure much higher, at 60,000 deaths, which Mr Tucker claims is "grossly overstated […] for propaganda purposes".
Former ambassador Mr Hopton said: "Already, a lot more people have been killed in these protests than at any time since the 1979 revolution. But we just don't know the statistics yet."
Human rights organisations said at least 550 people died in protests following the death of Mahsa Amini in 2022, while Iranian authorities claimed the figure was lower at 202.
Yet the scale of fatalities in the latest protests is, by the authorities' own admission, undoubtedly larger than in 2022 - leading Dr Rahmani-Rad to call the brutality "unprecedented in history".
"The only thing I can do is hope that the world becomes aware of what happened in Iran, that people around the world understand exactly what took place," he told Sky News.
Sky News has approached the Iranian embassy for confirmation of the number of people killed, but received no response.
The Data x Forensics team is a multi-skilled unit dedicated to providing transparent journalism from Sky News. We gather, analyse and visualise data to tell data-driven stories. We combine traditional reporting skills with advanced analysis of satellite images, social media and other open source information. Through multimedia storytelling we aim to better explain the world while also showing how our journalism is done.
The neuroscience service at Addenbrooke's Hospital in Cambridge helps treat complex brain injuries and head trauma cases.
The hospital's trust, Cambridge University Hospitals (CUH), took the unusual step of ordering a "rapid but thorough" review which will look at a "number of clinical teams".
The review will be independent and carried out by two official health bodies.
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It comes just months after Sky News revealed another investigation at the same hospital into a suspended orthopaedic paediatric surgeon.
An independent review was ordered into Kuldeep Stohr last year after serious issues were found with some of her surgeries on children.
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The report found the trust had missed multiple opportunities to act on concerns raised about her surgeries.
Addenbrooke's is a world-renowned hospital benefitting from the prestige of close associations with Cambridge University.
'The review is examining a number of clinical teams'
The rapid independent investigation into the neuroscience service will finish by the end of February, with the findings sent to the trust by the summer. CUH says it will publish the results and act on all the recommendations.
It's understood the review will look at the whole service and not one individual.
A CUH spokesperson said: "Patient safety is our highest priority. We continually review outcomes across our services to identify where improvements can be made and to ensure patients receive the best possible care.
"The review is examining a number of clinical teams to identify opportunities to strengthen clinical governance arrangements."